63P - Homology between cancer and viral epitopes as criteria to design improved cancer vaccines (63P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Cancer Immunology and Immunotherapy
Head and Neck Cancers
Presenter Cristian Capasso
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors C. Capasso1, T. Whalley2, V.S. Marwah3, A. Serafin4, M. Fusciello1, S. Feola1, B. Martins1, D. Greco3, B. Szomolay2, V. Cerullo1
  • 1Faculty Of Pharmacy, University of Helsinki, 00790 - Helsinki/FI
  • 2School Of Medicine, Cardiff University, CF103AT - Cardiff/GB
  • 3Institute Of Biotechnology, University of Helsinki, 00790 - Helsinki/FI
  • 4Faculty Of Pharmacy, University of Bologna, 40126 - Bologna/IT

Abstract

Background

Researchers have reported a link between several autoimmune reactions and viral infections. In fact, viral antigens can activate cross-reactive T-cells. We hypothesize that the similarity of a tumor peptide with a viral one can be used as a novel selection criteria when designing cancer vaccine therapies in order to engage a wider range of antigen-specific lymphocytes.

Methods

The EpitOME is a novel in silico platform that can compare a tumor protein sequence to an extensive library of viral peptides evaluating HLA-affinity, T-cells cross reactivity and sequence homology. We selected viral sequences that were predicted to be very similar with melanoma epitopes and used them to immunize mice. Animals were then challenged with B16 melanomas and tumor growth was fallowed. ELISPOT assays were used to evaluate the cross-reactivity between the viral and tumor-specific peptides.

Results

To test if viral epitopes can cross-react with tumor ones, we immunized mice with viral peptides resembling TRP2, TYR1 or gp100 antigens. We observed strong cross-reactivity by ELISPOT assays, thus confirming the underlying immunological mechanism. When we challenged these mice with melanoma cells, we observed a slower growth in immunized mice compared to the näive group. Interestingly, targeting TRP2 or gp100 antigens with viral sequences resulted in a remarkable control of the tumor growth.

Conclusions

Taken together, we demonstrated that the degree of similarity between tumor and viral antigens is an important aspect to take into account. The possibility to evoke strong anti-tumor responses by using viral peptides is important for the engagement of anti-tumor T-cells. In addition, the degree of “foreignness” of tumor epitopes can be used as selection criteria when screening peptides list from immunopeptidome analysis, helping in the selection of candidates for cancer vaccines.

Clinical trial identification

Legal entity responsible for the study

Cristian Capasso

Funding

None

Disclosure

All authors have declared no conflicts of interest.