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

Publication ,  Conference
Crosby, EJ; Gwin, WR; Chang, S; Maecker, HT; Lubkov, V; Snyder, JC; Broadwater, G; Hyslop, T; Osada, T; Hobeika, AC; Hartman, ZC; Morse, MA ...
Published in: Cancer Research
February 15, 2019

Background: Immune-based therapy for metastatic breast cancer has had limited success. Strategies to augment adaptive immunity include vaccines targeting genomic amplifications like Human Epidermal Growth Factor Type 2 (HER2), an established driver of malignancy. Using a novel alphaviral vector, we constructed a vaccine encoding a portion of HER2 (VRP-HER2).Methods: In preclinical studies, mice were immunized before or after implantation of hHER2+ tumor cells and HER2-specific immune responses and anti-tumor function were assessed. We then translated this vaccine into a phase I clinical trial in which subjects with advanced HER2-overexpressing breast cancers received VRP-HER2 every 2 weeks for a total of three doses (cohort 1). In cohort 2, subjects received the same dose of VRP-HER2 along with a standard HER2 targeted therapy.Results: VRP-HER2 induced HER2-specific T cell and antibody responses while controlling tumor growth in murine models. Vaccination with VRP-HER2 was well tolerated in both patient cohorts. PFS was modest, while median OS was 50.2 months in cohort 1 and 32.7 months in cohort 2. In cohort 2, there is one partial response and two patients with continued stable disease. Vaccine induced anti-HER2 antibodies and T cells were identified. Increased perforin expression by memory CD8 T cells post vaccination significantly correlated with improved PFS.Conclusions: VRP-HER2 led to an increase in perforin expressing HER2-specific memory CD8 T cells in preclinical and clinical studies, and had profound antitumor effects in murine models. The generation of HER2-specific memory CD8 T cells was significantly correlated with increased PFS in patients. Subsequent studies will seek to enhance T cell activity by combination with anti-PD-1/PD-L1 antibodies.Citation Format: Crosby EJ, Gwin WR, Chang S, Maecker HT, Lubkov V, Snyder JC, Broadwater G, Hyslop T, Osada T, Hobeika AC, Hartman ZC, Morse MA, Lyerly HK. CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-16.

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

February 15, 2019

Volume

79

Issue

4_Supplement

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
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Crosby, E. J., Gwin, W. R., Chang, S., Maecker, H. T., Lubkov, V., Snyder, J. C., … Lyerly, H. K. (2019). Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients. In Cancer Research (Vol. 79). American Association for Cancer Research (AACR). https://doi.org/10.1158/1538-7445.sabcs18-p2-09-16
Crosby, E. J., W. R. Gwin, S. Chang, H. T. Maecker, V. Lubkov, J. C. Snyder, G. Broadwater, et al. “Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients.” In Cancer Research, Vol. 79. American Association for Cancer Research (AACR), 2019. https://doi.org/10.1158/1538-7445.sabcs18-p2-09-16.
Crosby EJ, Gwin WR, Chang S, Maecker HT, Lubkov V, Snyder JC, et al. Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients. In: Cancer Research. American Association for Cancer Research (AACR); 2019.
Crosby, E. J., et al. “Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients.” Cancer Research, vol. 79, no. 4_Supplement, American Association for Cancer Research (AACR), 2019. Crossref, doi:10.1158/1538-7445.sabcs18-p2-09-16.
Crosby EJ, Gwin WR, Chang S, Maecker HT, Lubkov V, Snyder JC, Broadwater G, Hyslop T, Osada T, Hobeika AC, Hartman ZC, Morse MA, Lyerly HK. Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients. Cancer Research. American Association for Cancer Research (AACR); 2019.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

February 15, 2019

Volume

79

Issue

4_Supplement

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis