Novel minigene vaccine stimulates CD8+ memory inflation to control growth of murine colorectal tumor

• Published in: The Journal of immunology (1950) Vol. 204; no. 1_Supplement; pp. 169 - 169.36
• Main Authors: Kwok, Jonathan, Kroon, Anna Maria Theresa, Chinnakannan, Senthil, de Lara, Cathy, Gileadi, Uzi, Cerundolo, Vincenzo, Klenerman, Paul, Lee, Lian Ni
• Format: Journal Article
• Language: English
• Published: 01.05.2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.169.36

Abstract Fundamental science Memory “inflation” describes the sustained accumulation of expanded pools of antigen-specific CD8+ T-cells, which occurs in certain persistent viral infections e.g. cytomegalovirus, and after vaccination with replication deficient adenoviral vectors. Inflating T cells are sustained at high frequencies, possess an effector memory phenotype and home to non-lymphoid tissues – characteristics which are desirable in anti-tumor responses. Use of minigene (epitope only) vaccines allows targeting of responses and reliable generation of strong memory inflation. To explore this, adenoviral vectors were designed to stimulate an anti-tumor response against the dominant antigen in CT26 tumors, AH1, either as a full length or peptide immunogen. Groups of mice were immunized with the minigene AH1 vector. Tumor growth and immune responses were monitored using prophylactic or therapeutic regimens. Results Our lab has previously demonstrated that minigene vaccines generate strong inflationary responses compared to a full-length vector. Compared to the controls, tumors from minigene-immunized mice grew at a significantly slower rate, and the intra-tumoral environment was enriched for functional effector cells. The presence of AH1-specific CD8+ T cell populations in peripheral blood correlated overall with the anti-tumor effect. Conclusions Inflationary CD8+ T cells can be targeted against tumor antigens using our adenovirus minigene approach. Such responses show anti-tumor activity in prophylactic and therapeutic settings. Further studies to assess the impact of increasing the breadth of targeting and the impact of checkpoint inhibition are ongoing.