Effective antitumor peptide vaccines can induce severe autoimmune pathology

Hussein Sultan, Jimena Trillo-Tinoco, Paulo Rodriguez, Esteban Celis

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Immunotherapy has shown a tremendous success in treating cancer. Unfortunately, this success is frequently associated with severe autoimmune pathology. In this study, we used the transgenic RIP-gp mouse model to assess the antitumor therapeutic benefit of peptide vaccination while evaluating the possible associated autoimmune pathology. We report that palmitoylated gp33-41 peptide and poly-IC adjuvant vaccine (BiVax) generated ~ 5-10 % of antigen specific T cell responses in wild type and supposedly immune tolerant RIP-gp mice. Boosting with BiVax in combination with αCD40 antibody (TriVax) or BiVax in combination with IL-2/ αIL-2 antibody complexes (IL2Cx) significantly increased the immune responses (~30- 50%). Interestingly, although both boosts were equally effective in generating vast T cell responses, BiVax/IL2Cx showed better control of tumor growth than TriVax. However, this effect was associated with high incidence of diabetes in an antigen and CD8 dependent fashion. T cell responses generated by BiVax/IL2Cx, but not those generated by TriVax were highly resistant to PD-1/PD-L1 inhibitory signals. Nevertheless, PD-1 blockade enhanced the ability of TriVax to control tumor growth but increased the incidence of diabetes. Finally, we show that severe autoimmunity by BiVax/IL2Cx was prevented while preserving outstanding antitumor responses by utilizing a tumor antigen not expressed in the pancreas. Our data provides a clear evidence that peptide based vaccines can expand vast endogenous T cell responses which effectively control tumor growth but with high potential of autoimmune pathology.

Original languageEnglish (US)
Pages (from-to)70317-70331
Number of pages15
JournalOncotarget
Volume8
Issue number41
DOIs
Publication statusPublished - Jan 1 2017

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Keywords

  • Anti-CD40
  • Anti-tumor effect
  • Diabetes
  • IL-2 complex
  • Peptide vaccine

ASJC Scopus subject areas

  • Oncology

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