Oncotarget

Research Papers:

Effective antitumor peptide vaccines can induce severe autoimmune pathology

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

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Oncotarget. 2017; 8:70317-70331. https://doi.org/10.18632/oncotarget.19688

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Abstract

Hussein Sultan1,2, Jimena Trillo-Tinoco1, Paulo Rodriguez1 and Esteban Celis1,2

1Cancer Immunology, Immunotherapy and Tolerance Program, Georgia Cancer Center, Augusta University, Augusta, GA, USA

2Biochemistry and Cancer Biology Department, Georgia Cancer Center, Augusta University, Augusta, GA, USA

Correspondence to:

Esteban Celis, email: [email protected]

Keywords: peptide vaccine, anti-tumor effect, diabetes, IL-2 complex, anti-CD40

Received: May 12, 2017     Accepted: June 26, 2017     Published: July 29, 2017

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.


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