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Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients.

Publication ,  Journal Article
Morse, MA; Chapman, R; Powderly, J; Blackwell, K; Keler, T; Green, J; Riggs, R; He, L-Z; Ramakrishna, V; Vitale, L; Zhao, B; Butler, SA ...
Published in: Clin Cancer Res
July 15, 2011

PURPOSE: The use of tumor-derived proteins as cancer vaccines is complicated by tolerance to these self-antigens. Tolerance may be broken by immunization with activated, autologous, ex vivo generated and antigen-loaded, antigen-presenting cells (APC); however, targeting tumor antigen directly to APC in vivo would be a less complicated strategy. We wished to test whether targeted delivery of an otherwise poorly immunogenic, soluble antigen to APC through their mannose receptors (MR) would induce clinically relevant immunity. EXPERIMENTAL DESIGN: Two phase I studies were conducted with CDX-1307, a vaccine composed of human chorionic gonadotropin beta-chain (hCG-β) fused to an MR-specific monoclonal antibody, administered either locally (intradermally) or systemically (intravenously) in patients with advanced epithelial malignancies. An initial dose escalation of single-agent CDX-1307 was followed by additional cohorts of CDX-1307 combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) and the Toll-like receptor (TLR) 3 agonist polyinosinic-polycytidylic acid (poly-ICLC) and TLR7/8 agonist resiquimod to activate the APC. RESULTS: CDX-1307 induced consistent humoral and T-cell responses to hCG-β when coadministered with TLR agonists. Greater immune responses and clinical benefit, including the longest duration of stable disease, were observed with immunization combined with local TLR agonists. Immune responses were induced equally efficiently in patients with elevated and nonelevated levels of serum hCG-β. Antibodies within the serum of vaccinated participants had tumor suppressive function in vitro. Toxicity consisted chiefly of mild injection site reactions. CONCLUSIONS: APC targeting and activation induce adaptive immunity against poorly immunogenic self-antigens which has implications for enhancing the efficacy of cancer immunotherapy.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

July 15, 2011

Volume

17

Issue

14

Start / End Page

4844 / 4853

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Toll-Like Receptors
  • Skin
  • Recombinant Fusion Proteins
  • Oncology & Carcinogenesis
  • Neoplasms
  • Neoplasm Staging
  • Male
  • Immunity, Humoral
  • Immunity, Cellular
 

Citation

APA
Chicago
ICMJE
MLA
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Morse, M. A., Chapman, R., Powderly, J., Blackwell, K., Keler, T., Green, J., … Lyerly, H. K. (2011). Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients. Clin Cancer Res, 17(14), 4844–4853. https://doi.org/10.1158/1078-0432.CCR-11-0891
Morse, Michael A., Robert Chapman, John Powderly, Kimberly Blackwell, Tibor Keler, Jennifer Green, Renee Riggs, et al. “Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients.Clin Cancer Res 17, no. 14 (July 15, 2011): 4844–53. https://doi.org/10.1158/1078-0432.CCR-11-0891.
Morse MA, Chapman R, Powderly J, Blackwell K, Keler T, Green J, et al. Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients. Clin Cancer Res. 2011 Jul 15;17(14):4844–53.
Morse, Michael A., et al. “Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients.Clin Cancer Res, vol. 17, no. 14, July 2011, pp. 4844–53. Pubmed, doi:10.1158/1078-0432.CCR-11-0891.
Morse MA, Chapman R, Powderly J, Blackwell K, Keler T, Green J, Riggs R, He L-Z, Ramakrishna V, Vitale L, Zhao B, Butler SA, Hobeika A, Osada T, Davis T, Clay T, Lyerly HK. Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients. Clin Cancer Res. 2011 Jul 15;17(14):4844–4853.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

July 15, 2011

Volume

17

Issue

14

Start / End Page

4844 / 4853

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Toll-Like Receptors
  • Skin
  • Recombinant Fusion Proteins
  • Oncology & Carcinogenesis
  • Neoplasms
  • Neoplasm Staging
  • Male
  • Immunity, Humoral
  • Immunity, Cellular