Scholars@Duke
Zachary Conrad Hartman

Zachary Conrad Hartman

Associate Professor in Surgery
Surgery, Surgical Sciences
zachary.hartman@duke.edu
Box 2606 Med Ctr, Durham, NC 27710
Research Drive, MSRBI Rm 414, Durham, NC 27710

Selected Publications

CD27 agonism enhances long-lived CD4 T cell vaccine responses critical for antitumor immunity.

Journal Article Sci Immunol · December 19, 2025 Tumor antigen vaccination represents an appealing approach for cancer but has failed to materialize as oncologic standard of care. To understand long-term vaccine efficacy, we conducted a retrospective analysis of patients with human epidermal growth recep ... Full text Link to item Cite

TuNa-AI: A Hybrid Kernel Machine To Design Tunable Nanoparticles for Drug Delivery.

Journal Article ACS Nano · September 23, 2025 Artificial intelligence (AI) has the potential to transform nanoparticle development for drug delivery; however, existing strategies typically optimize either material selection or component ratios in isolation. To enable simultaneous optimization of both, ... Full text Link to item Cite

Effective extracellular payload release and immunomodulatory interactions govern the therapeutic effect of trastuzumab deruxtecan (T-DXd).

Journal Article Nat Commun · April 2, 2025 Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) targeting HER2, exhibiting significant clinical efficacy in breast cancer (BC) with varying HER2 expression, including HER2-low and HER2-ultralow. However, the precise mechanism underlying ... Full text Link to item Cite

Progesterone receptor-dependent downregulation of MHC class I promotes tumor immune evasion and growth in breast cancer.

Journal Article J Immunother Cancer · March 18, 2025 BACKGROUND: Breast cancer (BC) continues to be a major health concern with 250,000 new cases diagnosed annually in the USA, 75% of which are hormone receptor positive (HR+), expressing estrogen receptor alpha (ER) and/or the progesterone receptor (PR). Alt ... Full text Link to item Cite

Vaccines targeting ESR1 activating mutations elicit anti-tumor immune responses and suppress estrogen signaling in therapy resistant ER+ breast cancer.

Journal Article Hum Vaccin Immunother · December 31, 2024 ER+ breast cancers (BC) are characterized by the elevated expression and signaling of estrogen receptor alpha (ESR1), which renders them sensitive to anti-endocrine therapy. While these therapies are clinically effective, prolonged treatment inevitably res ... Full text Link to item Cite

Vaccination Against Androgen Receptor Splice Variants to Immunologically Target Prostate Cancer.

Journal Article Vaccines (Basel) · November 13, 2024 Background/Objectives: Androgen receptor (AR) expression and signaling are critical for the progression of prostate cancer and have been the therapeutic focus of prostate cancer for over 50 years. While a variety of agents have been developed to target thi ... Full text Link to item Cite

Abstract PO3-26-06: A self-replicating RNA Precision Immunotherapeutic for Overcoming Resistance to Endocrine Therapy in Estrogen Receptor Positive Breast Cancer (ER+BC)

Conference Cancer Research · May 2, 2024 AbstractAdvanced or metastatic ER+HER2- breast cancer (ER+BC) is an incurable disease. Standard 1L therapy (SOC) utilizes endocrine blockade with a nonsteroidal aromatase inhibitor (NSAI) combined with a CDK ... Full text Cite

FIGURE 2 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Mutant GFP and luciferase induce immune responses comparable with wild-type (WT) proteins. <b>A,</b> WT male Balb/c mice were vaccinated with Ad encoding WT or mutant copies of GFP (ΔT64; <i>n</i> = 5/group) and ser ... Full text Cite

Figure S2 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Validating mutant GFP and Luc activity in Adenovirus vaccines</p> ... Full text Cite

FIGURE 7 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Summary of tumor behavior in differentially tolerant animal models. <b>A,</b> Xenoantigen-bearing tumor cells implanted orthotopically into immune-deficient mice typically grow and metastasize as expected and can be easily obse ... Full text Cite

FIGURE 6 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>NoGlow mice reveal unappreciated metastatic dynamics independent of the primary tumor. <b>A,</b> Tumor growth of triple transgenic (3 ×) B16-F10 cells (10<sup>5</sup>) after subcutaneous implantation into the flank ... Full text Cite

FIGURE 5 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Tumor cells expressing GFP, rtTA, and Luciferase successfully engraft in NoGlow mice. <b>A,</b> Diagram of triple-transgenic (3 ×) E0771 cells. GFP and rtTA are constitutively expressed and Luc is induced with the addition of d ... Full text Cite

FIGURE 6 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>NoGlow mice reveal unappreciated metastatic dynamics independent of the primary tumor. <b>A,</b> Tumor growth of triple transgenic (3 ×) B16-F10 cells (10<sup>5</sup>) after subcutaneous implantation into the flank ... Full text Cite

Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent "NoGlow" Mice.

Journal Article Cancer Res Commun · April 9, 2024 UNLABELLED: The ability to temporally regulate gene expression and track labeled cells makes animal models powerful biomedical tools. However, sudden expression of xenobiotic genes [e.g., GFP, luciferase (Luc), or rtTA3] can trigger inadvertent immunity th ... Full text Link to item Cite

Figure S4 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Confirming triple-transgenic GFP rtTA-Luc construct in E0771 cells</p> ... Full text Cite

FIGURE 4 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>NoGlow mice reveal the impact of sex and tissue distribution on immune tolerance. <b>A,</b> Male WT (<i>n</i> = 3), CAG Luc-GFP (<i>n</i> = 3), and NoGlow+ (<i>n</i> = 6) or NoGlow− (<i&gt ... Full text Cite

Figure S1 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Additional E0771 tumor growth in WT, GH, and CAG Luc-GFP mice; MMTV CAG HER2 Ad-HER2 vaccination T cell responses.</p> ... Full text Cite

FIGURE 7 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Summary of tumor behavior in differentially tolerant animal models. <b>A,</b> Xenoantigen-bearing tumor cells implanted orthotopically into immune-deficient mice typically grow and metastasize as expected and can be easily obse ... Full text Cite

Data from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <div>Abstract<p>The ability to temporally regulate gene expression and track labeled cells makes animal models powerful biomedical tools. However, sudden expression of xenobiotic genes [e.g., GFP, luciferase (Luc), or rtTA3] can trigger ... Full text Cite

Data from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <div>Abstract<p>The ability to temporally regulate gene expression and track labeled cells makes animal models powerful biomedical tools. However, sudden expression of xenobiotic genes [e.g., GFP, luciferase (Luc), or rtTA3] can trigger ... Full text Cite

FIGURE 1 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Tolerance to foreign antigens is animal model specific. <b>A</b> and <b>B,</b> Mice expressing GFP and Luc in the pituitary (GH; <i>n</i> = 5), full-body GFP, and Luc (CAG Luc-GFP; <i>n</i> = ... Full text Cite

FIGURE 3 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>NoGlow mice express eGFP and Luciferase without background fluorescence and bioluminescence. <b>A,</b> Diagram of the NoGlow construct. LoxP-flanked stop site prevents expression of the NoGlow construct in the absence of Cre re ... Full text Cite

FIGURE 4 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>NoGlow mice reveal the impact of sex and tissue distribution on immune tolerance. <b>A,</b> Male WT (<i>n</i> = 3), CAG Luc-GFP (<i>n</i> = 3), and NoGlow+ (<i>n</i> = 6) or NoGlow− (<i&gt ... Full text Cite

FIGURE 5 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Tumor cells expressing GFP, rtTA, and Luciferase successfully engraft in NoGlow mice. <b>A,</b> Diagram of triple-transgenic (3 ×) E0771 cells. GFP and rtTA are constitutively expressed and Luc is induced with the addition of d ... Full text Cite

Figure S4 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Confirming triple-transgenic GFP rtTA-Luc construct in E0771 cells</p> ... Full text Cite

FIGURE 3 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>NoGlow mice express eGFP and Luciferase without background fluorescence and bioluminescence. <b>A,</b> Diagram of the NoGlow construct. LoxP-flanked stop site prevents expression of the NoGlow construct in the absence of Cre re ... Full text Cite

FIGURE 1 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Tolerance to foreign antigens is animal model specific. <b>A</b> and <b>B,</b> Mice expressing GFP and Luc in the pituitary (GH; <i>n</i> = 5), full-body GFP, and Luc (CAG Luc-GFP; <i>n</i> = ... Full text Cite

FIGURE 2 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Mutant GFP and luciferase induce immune responses comparable with wild-type (WT) proteins. <b>A,</b> WT male Balb/c mice were vaccinated with Ad encoding WT or mutant copies of GFP (ΔT64; <i>n</i> = 5/group) and ser ... Full text Cite

Figure S2 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Validating mutant GFP and Luc activity in Adenovirus vaccines</p> ... Full text Cite

Figure S1 from Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent “NoGlow” Mice

Other · April 9, 2024 <p>Additional E0771 tumor growth in WT, GH, and CAG Luc-GFP mice; MMTV CAG HER2 Ad-HER2 vaccination T cell responses.</p> ... Full text Cite

CEA vaccines.

Journal Article Hum Vaccin Immunother · December 15, 2023 Carcinoembryonic antigen (CEA) is a glycosylated cell surface oncofetal protein involved in adhesion, proliferation, and migration that is highly upregulated in multiple carcinomas and has long been a promising target for cancer vaccination. This review su ... Full text Link to item Cite

Dormant tumors circumvent tumor-specific adaptive immunity by establishing a Treg-dominated niche via DKK3.

Journal Article JCI Insight · November 22, 2023 Approximately 30% of breast cancer survivors deemed free of disease will experience locoregional or metastatic recurrence even up to 30 years after initial diagnosis, yet how residual/dormant tumor cells escape immunity elicited by the primary tumor remain ... Full text Link to item Cite

Beyond Neoantigens: Antigens Derived from Tumor Drivers as Cancer Vaccine Targets.

Journal Article Clin Cancer Res · September 1, 2023 A vaccine targeting HER2, a nonmutated but overexpressed tumor antigen, readily primed T cells for ex vivo expansion and adoptive transfer with minimal toxicity. This regimen led to intramolecular epitope spreading in a majority of patients and offers a tr ... Full text Link to item Cite

Cancer vaccine strategies using self-replicating RNA viral platforms.

Journal Article Cancer Gene Ther · June 2023 The development and success of RNA-based vaccines targeting SARS-CoV-2 has awakened new interest in utilizing RNA vaccines against cancer, particularly in the emerging use of self-replicating RNA (srRNA) viral vaccine platforms. These vaccines are based on ... Full text Link to item Cite

Clinical trials of self-replicating RNA-based cancer vaccines.

Journal Article Cancer Gene Ther · June 2023 Therapeutic cancer vaccines, designed to activate immune effectors against tumor antigens, utilize a number of different platforms for antigen delivery. Among these are messenger RNAs (mRNA), successfully deployed in some prophylactic SARS-CoV2 vaccines. T ... Full text Link to item Cite

Oncofetal protein glypican-3 is a biomarker and critical regulator of function for neuroendocrine cells in prostate cancer.

Journal Article J Pathol · May 2023 Neuroendocrine (NE) cells comprise ~1% of epithelial cells in benign prostate and prostatic adenocarcinoma (PCa). However, they become enriched in hormonally treated and castration-resistant PCa (CRPC). In addition, close to 20% of hormonally treated tumor ... Full text Link to item Cite

Abstract 2732: A self-replicating RNA precision medicine approach to therapeutic protein delivery of narrow therapeutic index biomolecules

Conference Cancer Research · April 4, 2023 AbstractProtein drug replacement using nucleic acid technologies has been a sought-after solution for in situ production of proteins with poor half-lives and challenging manufacturability. Linear mRNA approa ... Full text Cite

Abstract 6403: A self-replicating RNA precision medicine approach to overcoming resistance to endocrine therapy in ER+BC

Conference Cancer Research · April 4, 2023 AbstractDrug resistance remains the major driving factor behind the clinical failure of targeted therapeutics. Current oncology precision medicine approaches rely on targeting known acquired resistance mutat ... Full text Cite

Movie 1 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 labelled sidebuds. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p><p></p> ... Full text Cite

Movie 3 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 invasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 4 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 microinvasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 5 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 mammary intraepithelial neoplasm. d16HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 2 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 labelled sidebuds. d16HER2 shown in yellow. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 4 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 microinvasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Supplementary Tables 1-5 for scRNAseq marker genes from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>Supplementary Table 1: Cluster-specific markers from all cells (8,486 cells) Supplementary Table 2: Cluster-specific markers from all epithelial cells (3,843 cells) Supplementary Table 3: Cluster-specific markers from all immune cells (1,8 ... Full text Cite

Movie 5 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 mammary intraepithelial neoplasm. d16HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 1 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 labelled sidebuds. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p><p></p> ... Full text Cite

Data from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <div>Abstract<p>HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor het ... Full text Cite

Movie 3 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 invasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Supplementary Tables 1-5 for scRNAseq marker genes from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>Supplementary Table 1: Cluster-specific markers from all cells (8,486 cells) Supplementary Table 2: Cluster-specific markers from all epithelial cells (3,843 cells) Supplementary Table 3: Cluster-specific markers from all immune cells (1,8 ... Full text Cite

Movie 2 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 labelled sidebuds. d16HER2 shown in yellow. Krt14 antibody staining shown in green.</p> ... Full text Cite

Data from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <div>Abstract<p>HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor het ... Full text Cite

Data from IL26, a Noncanonical Mediator of DNA Inflammatory Stimulation, Promotes TNBC Engraftment and Progression in Association with Neutrophils

Other · March 31, 2023 <div>Abstract<p>IL26 is a unique amphipathic member of the IL10 family of cytokines that participates in inflammatory signaling through a canonical receptor pathway. It also directly binds DNA to facilitate cellular transduction and int ... Full text Cite

Combined Supplementary Figures from IL26, a Noncanonical Mediator of DNA Inflammatory Stimulation, Promotes TNBC Engraftment and Progression in Association with Neutrophils

Other · March 31, 2023 <p>SF1: IL-26 protein or mRNA expression in human cell lines and clinical samples; SF2: Single-cell profiling of CD4+ TH17 cells in TNBC patients; SF3: Confirmation of IL-26 knockdown in MDA-MB-231 cells; SF4: In vitro proliferation and in vi ... Full text Cite

Combined Supplementary Figures from IL26, a Noncanonical Mediator of DNA Inflammatory Stimulation, Promotes TNBC Engraftment and Progression in Association with Neutrophils

Other · March 31, 2023 <p>SF1: IL-26 protein or mRNA expression in human cell lines and clinical samples; SF2: Single-cell profiling of CD4+ TH17 cells in TNBC patients; SF3: Confirmation of IL-26 knockdown in MDA-MB-231 cells; SF4: In vitro proliferation and in vi ... Full text Cite

Figure S4 from Vaccine-Induced Memory CD8<sup>+</sup> T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study

Other · March 31, 2023 <p>Individual histograms of perforin expression by memory CD8 T cell cluster pre- and post-vaccination</p> ... Full text Cite

Table S2 from Vaccine-Induced Memory CD8<sup>+</sup> T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study

Other · March 31, 2023 <p>Concurrent HER2 therapies for each patient for whom CYTOF analysis was done</p> ... Full text Cite

Data from Vaccine-Induced Memory CD8<sup>+</sup> T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study

Other · March 31, 2023 <div>AbstractPurpose:<p>Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines ... Full text Cite

Figure S4 from Vaccine-Induced Memory CD8<sup>+</sup> T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study

Other · March 31, 2023 <p>Individual histograms of perforin expression by memory CD8 T cell cluster pre- and post-vaccination</p> ... Full text Cite

Data from Vaccine-Induced Memory CD8<sup>+</sup> T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study

Other · March 31, 2023 <div>AbstractPurpose:<p>Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines ... Full text Cite

Table S2 from Vaccine-Induced Memory CD8<sup>+</sup> T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study

Other · March 31, 2023 <p>Concurrent HER2 therapies for each patient for whom CYTOF analysis was done</p> ... Full text Cite

Data from IL26, a Noncanonical Mediator of DNA Inflammatory Stimulation, Promotes TNBC Engraftment and Progression in Association with Neutrophils

Other · March 31, 2023 <div>Abstract<p>IL26 is a unique amphipathic member of the IL10 family of cytokines that participates in inflammatory signaling through a canonical receptor pathway. It also directly binds DNA to facilitate cellular transduction and int ... Full text Cite

Data from Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer

Other · March 31, 2023 <div>AbstractPurpose:<p>Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had b ... Full text Cite

Data from Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer

Other · March 31, 2023 <div>AbstractPurpose:<p>Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had b ... Full text Cite

Abstract PR015: Dormant mammary tumors persist long-term despite adaptive immunity by establishing a Treg-dominated niche via DKK3

Conference Cancer Research · January 15, 2023 AbstractA significant portion of breast cancer survivors eventually experience locoregional or metastatic recurrence. It is clear that the adaptive immune system controls proliferative tumor outgrowth, but h ... Full text Cite

A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity.

Journal Article Cancers (Basel) · November 23, 2022 Ductal carcinoma in situ (DCIS) of the breast is often managed by lumpectomy and radiation or mastectomy, despite its indolent features. Effective non-invasive treatment strategies could reduce the morbidity of DCIS treatment. We have exploited the high he ... Full text Link to item Cite

Combination of a novel heat shock protein 90-targeted photodynamic therapy with PD-1/PD-L1 blockade induces potent systemic antitumor efficacy and abscopal effect against breast cancers.

Journal Article J Immunother Cancer · September 2022 BACKGROUND: We previously demonstrated potent antitumor activity against human breast cancer xenografts using photodynamic therapy (PDT) targeting a novel tumor-specific photosensitizer (HS201), which binds heat shock protein 90 (HS201-PDT). However, induc ... Full text Link to item Cite

Trastuzumab/pertuzumab combination therapy stimulates antitumor responses through complement-dependent cytotoxicity and phagocytosis.

Journal Article JCI Insight · March 22, 2022 Two HER2-specific mAbs, trastuzumab and pertuzumab (T+P), combined with chemotherapy comprise standard-of-care treatment for advanced HER2+ breast cancers (BC). While this antibody combination is highly effective, its synergistic mechanism-of-action (MOA) ... Full text Link to item Cite

Sensitizing immune unresponsive colorectal cancers to immune checkpoint inhibitors through MAVS overexpression.

Journal Article J Immunother Cancer · March 2022 BACKGROUND: The majority of colorectal carcinomas (CRCs) are insensitive to programmed death protein-1/programmed death-ligand 1 (anti-PD-1/PD-L1) immune checkpoint inhibitor (ICI) antibodies. While there are many causes for ICI insensitivity, recent studi ... Full text Link to item Cite

HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study.

Journal Article Mol Cancer Ther · January 2022 A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of n ... Full text Link to item Cite

Lauryn Werner

Conference CANCER RESEARCH · 2022 Cite

HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase.

Journal Article Mol Cancer Res · October 2021 HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the in ... Full text Link to item Cite

Mechanisms of Therapeutic Antitumor Monoclonal Antibodies.

Journal Article Cancer Res · September 15, 2021 Monoclonal antibodies (mAb) are a major component of cancer therapy. In this review, we summarize the different therapeutic mAbs that have been successfully developed against various tumor-expressed antigens and examine our current understanding of their d ... Full text Link to item Cite

Progesterone promotes immunomodulation and tumor development in the murine mammary gland.

Journal Article J Immunother Cancer · May 2021 BACKGROUND: Clinical studies have linked usage of progestins (synthetic progesterone [P4]) to breast cancer risk. However, little is understood regarding the role of native P4, signaling through the progesterone receptor (PR), in breast tumor formation. Re ... Full text Link to item Cite

Long-term survival of patients with stage III colon cancer treated with VRP-CEA(6D), an alphavirus vector that increases the CD8+ effector memory T cell to Treg ratio.

Journal Article J Immunother Cancer · November 2020 BACKGROUND: There remains a significant need to eliminate the risk of recurrence of resected cancers. Cancer vaccines are well tolerated and activate tumor-specific immune effectors and lead to long-term survival in some patients. We hypothesized that vacc ... Full text Link to item Cite

Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.

Journal Article Clin Cancer Res · September 1, 2020 PURPOSE: Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we h ... Full text Link to item Cite

Abstract 904: Stimulation and expansion of oncogene-reactive tumor infiltrating T cells through combined Ad-HER2Δ16 vaccination and anti-PD1 enable anti-tumor responses against established HER2 BC

Conference Cancer Research · August 15, 2020 AbstractDespite promising advances, overcoming immune suppression and driving productive immune responses in the tumor microenvironment remains a significant challenge. Using a spontaneous breast cancer mode ... Full text Cite

IL26, a Noncanonical Mediator of DNA Inflammatory Stimulation, Promotes TNBC Engraftment and Progression in Association with Neutrophils.

Journal Article Cancer Res · August 1, 2020 IL26 is a unique amphipathic member of the IL10 family of cytokines that participates in inflammatory signaling through a canonical receptor pathway. It also directly binds DNA to facilitate cellular transduction and intracellular inflammatory signaling. A ... Full text Link to item Cite

HER2-LAMP vaccines effectively traffic to endolysosomal compartments and generate enhanced polyfunctional T cell responses that induce complete tumor regression.

Journal Article J Immunother Cancer · June 2020 BACKGROUND: The advent of immune checkpoint blockade antibodies has demonstrated that effective mobilization of T cell responses can cause tumor regression of metastatic cancers, although these responses are heterogeneous and restricted to certain histolog ... Full text Link to item Cite

Abstract B107: Dormant breast tumor cells avoid the adaptive immune system through regulation of the immune and tumor microenvironment

Conference Cancer Immunology Research · March 1, 2020 AbstractMany cancer survivors respond to early treatment with complete remission only to succumb to the disease after the tumor returns, sometimes decades later, in a distant metastatic site. Tumor cells can ... Full text Cite

CD47 blockade augmentation of trastuzumab antitumor efficacy dependent on antibody-dependent cellular phagocytosis.

Journal Article JCI Insight · December 19, 2019 The HER2-specific monoclonal antibody (mAb), trastuzumab, has been the mainstay of therapy for HER2+ breast cancer (BC) for approximately 20 years. However, its therapeutic mechanism of action (MOA) remains unclear, with antitumor responses to trastuzumab ... Full text Link to item Cite

T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes.

Journal Article Cell · August 8, 2019 T cell recognition of specific antigens mediates protection from pathogens and controls neoplasias, but can also cause autoimmunity. Our knowledge of T cell antigens and their implications for human health is limited by the technical limitations of T cell ... Full text Link to item Cite

Vaccine-Induced Memory CD8+ T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study.

Journal Article Clin Cancer Res · May 1, 2019 PURPOSE: Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines targeting established oncogenic dr ... Full text Open Access Link to item Cite

Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients

Conference Cancer Research · February 15, 2019 AbstractBackground: Immune-based therapy for metastatic breast cancer has had limited success. Strategies to augment adaptive immunity include vaccines targeting genomic amplifications like Human Epidermal G ... Full text Cite

Right Time and Place for IL12: Targeted Delivery Stimulates Immune Therapy.

Journal Article Clin Cancer Res · January 1, 2019 Systemic IL12 therapy has potent antitumor effects, but clinical delivery of this potent cytokine has been complicated by systemic toxicity. A novel strategy to deliver IL12 to the tumor microenvironment appears promising in a first-in-human study, appeari ... Full text Link to item Cite

Abstract A22: Augmentation of a novel adenoviral vaccine strategy by checkpoint inhibitors

Conference Cancer Immunology Research · September 1, 2018 AbstractThe immunologic hurdles for a vaccine targeting cancer are much higher than for those targeting an infectious disease. The profoundly immunosuppressive tumor microenvironment, the lack of microbial d ... Full text Cite

Polyfunctional anti-human epidermal growth factor receptor 3 (anti-HER3) antibodies induced by HER3 vaccines have multiple mechanisms of antitumor activity against therapy resistant and triple negative breast cancers.

Journal Article Breast Cancer Res · August 9, 2018 BACKGROUND: Upregulation of human epidermal growth factor receptor 3 (HER3) is a major mechanism of acquired resistance to therapies targeting its heterodimerization partners epidermal growth factor receptor (EGFR) and human epidermal growth factor recepto ... Full text Link to item Cite

Complimentary mechanisms of dual checkpoint blockade expand unique T-cell repertoires and activate adaptive anti-tumor immunity in triple-negative breast tumors.

Journal Article Oncoimmunology · 2018 Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating l ... Full text Link to item Cite

In Vivo Detection of HSP90 Identifies Breast Cancers with Aggressive Behavior.

Journal Article Clin Cancer Res · December 15, 2017 Purpose: Hsp90, a chaperone to numerous molecular pathways in malignant cells, is elevated in aggressive breast cancers. We hypothesized that identifying breast cells with elevated Hsp90 activity in situ could result in early detection of aggressive breast ... Full text Link to item Cite

An unbiased in vivo functional genomics screening approach in mice identifies novel tumor cell-based regulators of immune rejection.

Journal Article Cancer Immunol Immunother · December 2017 The clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, there ... Full text Link to item Cite

Abstract A38: Checkpoint blockade elicits unique T cell expansion to promote tumor regression

Conference Cancer Immunology Research · March 1, 2017 AbstractWhile PD-1 and CTLA-4 immune checkpoint antibodies have led to durable clinical activity in certain cancers, only a fraction of patients exhibit responses. In these responsive tumors, PD-1 and CTLA-4 ... Full text Cite

Abstract P2-04-27: CTLA-4 and PD-1 checkpoint inhibitors enhance individually tailored adaptive anti-tumor immune responses to overcome tumor immunosuppression and effectively treat triple-negative breast cancer

Conference Cancer Research · February 15, 2017 AbstractDespite a lack of unifying drivers in Triple-Negative Breast Cancer (TNBC), our lab and others have uncovered that these cancers have elevated expression of inflammatory genes and immunosuppressive m ... Full text Cite

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy.

Journal Article Oncoimmunology · 2017 Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-i ... Full text Link to item Cite

Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition.

Journal Article Oncoimmunology · 2017 Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicabil ... Full text Link to item Cite

The ErbB2ΔEx16 splice variant is a major oncogenic driver in breast cancer that promotes a pro-metastatic tumor microenvironment.

Journal Article Oncogene · November 24, 2016 Amplification and overexpression of erbB2/neu proto-oncogene is observed in 20-30% human breast cancer and is inversely correlated with the survival of the patient. Despite this, somatic activating mutations within erbB2 in human breast cancers are rare. H ... Full text Link to item Cite

Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion.

Journal Article Breast Cancer Res Treat · August 2016 Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-n ... Full text Link to item Cite

Death-associated protein kinase 1 promotes growth of p53-mutant cancers.

Journal Article J Clin Invest · July 1, 2015 Estrogen receptor-negative (ER-negative) breast cancers are extremely aggressive and associated with poor prognosis. In particular, effective treatment strategies are limited for patients diagnosed with triple receptor-negative breast cancer (TNBC), which ... Full text Link to item Cite

Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

Journal Article J Immunother · May 2015 Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optim ... Full text Link to item Cite

Optical and radioiodinated tethered Hsp90 inhibitors reveal selective internalization of ectopic Hsp90 in malignant breast tumor cells.

Journal Article Chem Biol · September 19, 2013 Inhibitors of heat-shock protein 90 (Hsp90) have demonstrated an unusual selectivity for tumor cells despite its ubiquitous expression. This phenomenon has remained unexplained, but could be influenced by ectopically expressed Hsp90 in tumors. In this work ... Full text Link to item Cite

Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8.

Journal Article Cancer Res · June 1, 2013 Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In T ... Full text Link to item Cite

A SUMOylation-dependent transcriptional subprogram is required for Myc-driven tumorigenesis

Journal Article Science · January 20, 2012 Myc is an oncogenic transcription factor frequently dysregulated in human cancer. To identify pathways supporting the Myc oncogenic program, we used a genome-wide RNA interference screen to search for Myc - synthetic lethal genes and uncovered a role for t ... Full text Cite

Increasing vaccine potency through exosome antigen targeting.

Journal Article Vaccine · November 21, 2011 While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to e ... Full text Link to item Cite

Truncated ErbB2 expressed in tumor cell nuclei contributes to acquired therapeutic resistance to ErbB2 kinase inhibitors.

Journal Article Mol Cancer Ther · August 2011 ErbB2 tyrosine kinase inhibitors (TKI) block tyrosine autophosphorylation and activation of the full-length transmembrane ErbB2 receptor (p185(ErbB2)). In addition to p185(ErbB2), truncated forms of ErbB2 exist in breast cancer cell lines and clinical tumo ... Full text Link to item Cite

HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis.

Journal Article Cancer Res · July 1, 2011 HER2 overexpression occurs in approximately 25% of breast cancers, where it correlates with poor prognosis. Likewise, systemic inflammation in breast cancer correlates with poor prognosis, although the process is not understood. In this study, we explored ... Full text Link to item Cite

Polyclonal immune responses to antigens associated with cancer signaling pathways and new strategies to enhance cancer vaccines.

Journal Article Immunol Res · April 2011 Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been among the most successful. A challenge for these ther ... Full text Link to item Cite

Ligand-independent toll-like receptor signals generated by ectopic overexpression of MyD88 generate local and systemic antitumor immunity.

Journal Article Cancer Res · September 15, 2010 Although critical for initiating and regulating immune responses, the therapeutic use of individual cytokines as anticancer immunotherapeutic agents has achieved only modest clinical success. Consequently, many current strategies have focused on the use of ... Full text Link to item Cite

Adenovirus capsid-display of the retro-oriented human complement inhibitor DAF reduces Ad vector-triggered immune responses in vitro and in vivo.

Journal Article Blood · September 9, 2010 Adenovirus (Ad) vectors are widely used in human clinical trials. However, at higher dosages, Ad vector-triggered innate toxicities remain a major obstacle to many applications. Ad interactions with the complement system significantly contribute to innate ... Full text Link to item Cite

Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA.

Journal Article Cancer Immunol Immunother · July 2010 Adenovirus serotype 5 (Ad5) has been widely used in clinical trials because it expresses inserted transgenes robustly and augments the innate immune response. Strategies to improve Ad5 vectors that can circumvent Ad5 immunity have become a critical issue, ... Full text Link to item Cite

Synergism from combined immunologic and pharmacologic inhibition of HER2 in vivo.

Journal Article Int J Cancer · June 15, 2010 The monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib improve the clinical outcome of patients with HER2-overexpressing breast cancer. However, the majority of metastatic cancers will eventually progress, suggesting the ... Full text Link to item Cite

An adenoviral vaccine encoding full-length inactivated human Her2 exhibits potent immunogenicty and enhanced therapeutic efficacy without oncogenicity.

Journal Article Clin Cancer Res · March 1, 2010 PURPOSE: Overexpression of the breast cancer oncogene HER2 correlates with poor survival. Current HER2-directed therapies confer limited clinical benefits and most patients experience progressive disease. Because refractory tumors remain strongly HER2+, va ... Full text Link to item Cite

Novel adenovirus vectors 'capsid-displaying' a human complement inhibitor.

Journal Article J Innate Immun · 2010 Adenovirus (Ad) vectors are currently the most commonly utilized gene transfer vectors in humans worldwide. Unfortunately, upon contact with the circulatory system, Ads induce several, innate, complement-dependent toxicities that limit the full potential f ... Full text Link to item Cite

Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity.

Journal Article Cancer Gene Ther · September 2009 Recombinant serotype 5 adenovirus (Ad5) vectors lacking E1 expression induce robust immune responses against encoded transgenes in pre-clinical models, but have muted responses in human trials because of widespread pre-existing anti-adenovirus immunity. At ... Full text Link to item Cite

Induction of Wilms' tumor protein (WT1)-specific antitumor immunity using a truncated WT1-expressing adenovirus vaccine.

Journal Article Clin Cancer Res · April 15, 2009 PURPOSE: Wilms' tumor protein (WT1) is overexpressed in most leukemias and many solid tumors and is a promising target for tumor immunotherapy. WT1 peptide-based cancer vaccines have been reported but have limited application due to HLA restriction of the ... Full text Link to item Cite

The deacetylase HDAC4 controls myocyte enhancing factor-2-dependent structural gene expression in response to neural activity.

Journal Article FASEB J · January 2009 Histone deacetylase 4 (HDAC4) binds and inhibits activation of the critical muscle transcription factor myocyte enhancer factor-2 (MEF2). However, the physiological significance of the HDAC4-MEF2 complex in skeletal muscle has not been established. Here we ... Full text Link to item Cite

Replication-attenuated Human Adenoviral Type 4 vectors elicit capsid dependent enhanced innate immune responses that are partially dependent upon interactions with the complement system.

Journal Article Virology · May 10, 2008 Human Adenovirus Type 4 (HAdV-4) is responsible for epidemic outbreaks of Acute Respiratory Disease (especially in military recruits), and is known to cause significant morbidity with several reported cases of mortality. However, we do not understand why t ... Full text Link to item Cite

Adenovirus vector induced innate immune responses: impact upon efficacy and toxicity in gene therapy and vaccine applications.

Journal Article Virus Res · March 2008 Extensively characterized, modified, and employed for a variety of purposes, adenovirus (Ad) vectors are generally regarded as having great potential by many applied virologists who wish to manipulate and use viral biology to achieve beneficial clinical ou ... Full text Link to item Cite

Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells.

Journal Article Virology · February 20, 2007 Adenovirus vectors are known to induce certain genes and impact innate response networks, but a broad understanding of this process and its mechanisms is currently lacking. For this reason, we chose to investigate and characterize Ad innate immunity using ... Full text Link to item Cite

Adenovirus infection triggers a rapid, MyD88-regulated transcriptome response critical to acute-phase and adaptive immune responses in vivo.

Journal Article J Virol · February 2007 Nearly 50 years ago, the discovery of interferon prompted the notion that host cells innately respond to viral invasion. Since that time, technological advances have allowed this response to be extensively characterized and dissected in vitro. However, the ... Full text Link to item Cite

Multiple innate inflammatory responses induced after systemic adenovirus vector delivery depend on a functional complement system.

Journal Article Mol Ther · October 2006 Excessive complement activation can result in extreme tissue damage and systemic inflammatory responses, similar to innate immune responses rapidly elicited after systemic adenovirus (Ad) injections. To determine if Ad interactions with the complement syst ... Full text Link to item Cite

Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice.

Journal Article Mol Ther · January 2006 Glycogen storage disease type II (GSD-II) patients manifest symptoms of muscular dystrophy secondary to abnormal glycogen storage in cardiac and skeletal muscles. For GSD-II, we hypothesized that a fully deleted adenovirus (FDAd) vector expressing hGAA via ... Full text Link to item Cite