Skip to main content

Volume 3 Supplement 2

30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)

  • Poster presentation
  • Open access
  • Published:

Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T cell anergy and promotes survival in tumor-bearing mice

Immunotherapy is gathering momentum as a primary therapy for cancer patients. However, monotherapies have limited efficacy in improving outcomes and only benefit a subset of patients. Combination therapies targeting multiple pathways can augment an immune response to further improve survival. Here, we demonstrate that dual anti-OX40/anti-CTLA-4 immunotherapy generated a potent antigen-specific CD8 T cell response, enhancing expansion, effector function, and memory T cell persistence. Importantly, OX40 and CTLA-4 expression on CD8 T cells was critical to maximally promote their expansion following combination therapy. Animals treated with combination therapy and vaccination using anti-DEC-205-HER2 had significantly improved survival in a mammary carcinoma model. Vaccination with combination therapy uniquely restricted Th2-cytokine production by CD4 cells, relative to combination therapy alone, and enhanced IFNα production by CD8 and CD4 cells. We observed an increase in MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, and GM-CSF production by CD8 and CD4 T cells following treatment. Furthermore, this therapy was associated with extensive tumor destruction and T cell infiltration into the tumor. Notably, vaccination with combination therapy reversed anergy and enhanced the expansion and function of CD8 T cells recognizing a tumor-associated antigen in a spontaneous model of prostate adenocarcinoma. Collectively, these data demonstrate that the addition of an anti-DEC-205-HER2 vaccine with combined anti-OX40/anti-CTLA-4 immunotherapy augmented anti-tumor CD8 T cell function, while limiting Th2 polarization in CD4 cells and improving overall survival.

Author information

Authors and Affiliations


Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit

The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Linch, S., Kasiewicz, M.J., McNamara, M. et al. Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T cell anergy and promotes survival in tumor-bearing mice. j. immunotherapy cancer 3 (Suppl 2), P360 (2015).

Download citation

  • Published:

  • DOI: