Using ovalbumin (OVA) as a canonical neoantigen of the mouse, Karandikar et al. studied in vivo the immunogenicity and physiological presentation of predicted epitopes as epitope-length peptides or in the context of whole OVA, and identified several novel epitopes. Mice bearing progressing OVA-expressing E.G7 tumors showed no CD8+ responses to any OVA epitopes, including SIINFEKL, unless Tregs were depleted with an anti-CTLA-4 antibody. Prophylactic immunization with OVA or SIINFEKL, but not any other identified epitope, protected against E.G7 tumors, however, therapeutic vaccination with SIINFEKL did not reduce tumor growth.
MHC I-restricted epitopes of chicken ovalbumin (OVA) were originally identified using CD8 T cells as probes. Here, using bioinformatics tools, we identify four additional epitopes in OVA in addition to a cryptic epitope. Each new epitope is presented in vivo, as deduced from the lack of CD8 response to it in OVA-transgenic mice. In addition, CD8 responses to the known and novel epitopes are examined in C57BL/6 mice exposed to the OVA-expressing tumor E.G7 in several ways. No responses to any epitope including SIINFEKL are detected in mice with growing E.G7 or mice immunized with the tumor. Only in E.G7-bearing mice treated with an anti-CTLA4 antibody which depletes tumor-infiltrating regulatory T cells, CD8 responses to SIINFEKL and the novel epitope EKYNLTSVL are detected. Finally, all epitopes fails to treat mice with pre-existing tumors. These observations force an important re-consideration of the common assumptions about the therapeutic value of neoepitopes detected by CD8 responses in tumor-bearing hosts.
Author Info: (1) (2) (3) (4) (5) (6)
Author Info: (1) (2) (3) (4) (5) (6)
