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PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model.

Publication ,  Journal Article
Peng, S; Tan, M; Li, Y-D; Cheng, MA; Farmer, E; Ferrall, L; Gaillard, S; Roden, RBS; Hung, C-F; Wu, T-C
Published in: Cancer Immunol Immunother
April 2021

INTRODUCTION: The human papillomavirus (HPV) encoded oncoproteins E6 and E7 are constitutively expressed in HPV-associated cancers, making them logical therapeutic targets. Intramuscular immunization of patients with HPV16 L2E7E6 fusion protein vaccine (TA-CIN) is well tolerated and induces HPV-specific cellular immune responses. Efficacy of PD-1 immune checkpoint blockade correlates with the level of tumor-infiltrating CD8 + T cells, yet most patients lack significant tumor infiltration of immune cells making immune checkpoint blockade suboptimal. We hypothesized that intratumoral vaccination with TA-CIN could increase the number of tumor-infiltrating CD8 + T cells, synergize with PD-1 blockade and result in better control of tumors compared with either PD-1 blockade or vaccination alone. METHODS: We examined the immunogenicity and antitumor effects of intratumoral vaccination with TA-CIN alone or in combination with PD-1 blockade in the TC-1 syngeneic murine tumor model expressing HPV16 E6/E7. RESULTS: Intratumoral vaccination with TA-CIN induced stronger antigen-specific CD8 + T cell responses and antitumor effects. Intratumoral TA-CIN vaccination generated a systemic immune response that was able to control distal TC-1 tumors. Furthermore, intratumoral TA-CIN vaccination induced tumor infiltration of antigen-specific CD8 + T cells. Knockout of Batf3 abolished antigen-specific CD8 + T cell responses and antitumor effects of intratumoral TA-CIN vaccination. Finally, PD-1 blockade synergizes with intratumoral TA-CIN vaccination resulting in significantly enhanced antigen-specific CD8 + T cell responses and complete regression of tumors, whereas either alone failed to control established TC-1 tumor. CONCLUSIONS: Our results provide rationale for future clinical testing of intratumoral TA-CIN vaccination in combination with PD-1 blockade for the control of HPV16-associated tumors.

Duke Scholars

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Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

April 2021

Volume

70

Issue

4

Start / End Page

1049 / 1062

Location

Germany

Related Subject Headings

  • Vaccination
  • Uterine Cervical Neoplasms
  • Recombinant Fusion Proteins
  • Programmed Cell Death 1 Receptor
  • Papillomavirus E7 Proteins
  • Mice, Inbred C57BL
  • Mice
  • Lymphocytes, Tumor-Infiltrating
  • Immunology
  • Immunity, Cellular
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Peng, S., Tan, M., Li, Y.-D., Cheng, M. A., Farmer, E., Ferrall, L., … Wu, T.-C. (2021). PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model. Cancer Immunol Immunother, 70(4), 1049–1062. https://doi.org/10.1007/s00262-020-02754-x
Peng, Shiwen, Marietta Tan, Yen-Der Li, Max A. Cheng, Emily Farmer, Louise Ferrall, Stephanie Gaillard, Richard B. S. Roden, Chien-Fu Hung, and T. -. C. Wu. “PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model.Cancer Immunol Immunother 70, no. 4 (April 2021): 1049–62. https://doi.org/10.1007/s00262-020-02754-x.
Peng S, Tan M, Li Y-D, Cheng MA, Farmer E, Ferrall L, et al. PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model. Cancer Immunol Immunother. 2021 Apr;70(4):1049–62.
Peng, Shiwen, et al. “PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model.Cancer Immunol Immunother, vol. 70, no. 4, Apr. 2021, pp. 1049–62. Pubmed, doi:10.1007/s00262-020-02754-x.
Peng S, Tan M, Li Y-D, Cheng MA, Farmer E, Ferrall L, Gaillard S, Roden RBS, Hung C-F, Wu T-C. PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model. Cancer Immunol Immunother. 2021 Apr;70(4):1049–1062.
Journal cover image

Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

April 2021

Volume

70

Issue

4

Start / End Page

1049 / 1062

Location

Germany

Related Subject Headings

  • Vaccination
  • Uterine Cervical Neoplasms
  • Recombinant Fusion Proteins
  • Programmed Cell Death 1 Receptor
  • Papillomavirus E7 Proteins
  • Mice, Inbred C57BL
  • Mice
  • Lymphocytes, Tumor-Infiltrating
  • Immunology
  • Immunity, Cellular