Numerous CD8 T cell epitopes have been identified allowing the development of epitope-based cancer immunotherapy such as the use of synthetic peptide-based vaccines. However, peptide vaccines have been notoriously poorly immunogenic and provide suboptimal therapeutic effects. In contrast, as a response to viral and bacterial infections, the immune system has the capacity to produce huge numbers of antigen-specific T cells that eliminate disease and provide memory responses to prevent future infections. Our strategy to optimize peptide vaccines is to design immunization strategies that mimic these infections by providing the necessary immune activation signals together with the appropriate immunogenic peptide. Furthermore, it has been proposed that minimal peptide epitopes are poorly immunogenic because they are presented to T cells by non-professional APCs. Therefore, it is suggested that using long peptides vaccines will improve immunogenicity by forcing antigen presentation by professional APCs. Using several mouse tumor models, we observe that peptide composition (hydrophobicity, amphipathicity), adjuvant and route of vaccine administration are more critical than peptide size for generating strong CD8 T cell responses that limit tumor growth. Two separate events are required for peptides to generate massive CD8 T cell responses, similar to those observed during acute viral infections: 1) Peptide priming mediated professional APCs, where CD40 activation and TLR signals are critical; 2) T cell expansion, which can be mediated by either professional and non-professional APCs and where type-I interferon induced by retinoic acid-inducible (RIG-I)-like receptor stimulation by poly-IC plays a critical role. Effective anti-tumor CD8 T cell responses were accomplished by 2 systemic injections (iv or im 5-7 days apart) of peptide/poly-IC.
Citation Format: Esteban Celis. Designing cancer vaccines that mimic viral infections. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr IA16.
- ©2015 American Association for Cancer Research.