Research Interest: Viral and tumor immunology
Ph.D.: University of London
Postdoctoral: MRC National Institute for Medical Research, London, and the Scripps Research Institute, La Jolla
Dendritic cell vaccination for ovarian cancer
The finding that Th17 infiltration correlates with markedly prolonged overall survival among ovarian cancer patients offers a counterpoint to the known association of Treg infiltration with poor clinical outcomes, and prompts the question of whether Th17 cells could be induced or expanded to therapeutic advantage. We have shown that treatment of ovarian tumor antigen-loaded, cytokine-matured dendritic cells (DC) with a combination of IL-15 and a p38 MAPK inhibitor offers potent synergy in antagonism of Treg induction and redirection toward Th17 responses that correlate with strong CD8+ cytotoxic T lymphocyte activation, thus affording the opportunity for clinical trials of DC vaccination that promotes Th1/Th17 immunity. Our recently completed Phase I clinical trial of maintenance Th17-inducing DC vaccination for stage IIIC–IV ovarian cancer patients following initial surgery and chemotherapy (MS Block et al, Nature Communications, 2020) reported a correlation of T cell and antibody responses with recurrence-free survival (RFS). Of 18 evaluable patients, 39% remain recurrence-free with a median follow-up of 49.2 months’ post-enrollment, and overall survival was 55%.
The development of DC vaccination strategies to boost Th17 immunity in ovarian cancer patients represents a significant step forward, but there remains the question of whether DC vaccination alone would be sufficient to provide clinical benefit in the face of continuing local immune suppression in the tumor microenvironment. In partnership with investigators at MD Anderson Cancer Center, the Mayo Clinic and the University of Pennsylvania, our laboratory is focused on strategies that alleviate myeloid cell-mediated immune suppression and boost the efficacy of DC vaccination and other immunotherapies for ovarian cancer.
- Lamichhane, P., Karyampudi, L., Shreeder, B., Krempski, J., Bahr, D., Daum, J., Kalli, K.R., Goode, E.L., Block, M.S., Cannon, M.J., Knutson, K.L. 2017. IL-10 release upon PD-1 blockade sustains immunosuppression in ovarian cancer. Cancer Res. 77:6667-6678.
- Cannon, M.J., Block, M.S., Morehead, L.C., Knutson, K.L. 2019. The evolving clinical landscape for dendritic cell vaccines and cancer immunotherapy. Immunotherapy 11:75-79.
- Jenkins, S.V., Robeson, M.S., Griffin, R.J., Quick, C.M., Siegel, E.R., Cannon, M.J., Vang, K.B., Dings, R.P.M. 2019. Gastrointestinal tract dysbiosis enhances distal tumor progression through suppression of leukocyte trafficking. Cancer Res. 79:5999-6009.
- Block, M.S., Dietz, A.B., Gustafson, M.P., Kalli, K.R., Erskine, C.L., Youssef, B., Vijay, G.V., Allred, J.B., Pavelko, K.D., Strausbach, M.A., Lin, Y., Grudem, M.E., Jatoi, A., Klampe, C.M., Wahner-Hendrickson, A.E., Weroha, S.J., Glaser, G.E., Kumar, A., Langstraat, C.L., Solseth, M.L., Deeds, M.C., Knutson, K.L., Cannon, M.J. 2020. Th17-inducing autologous dendritic cell vaccination promotes cellular and humoral anti-tumor immunity in ovarian cancer patients. Nature Communications, 11:5173. https://doi.org/10.1038/s41467-020-18962-z
Dr. Cannon’s Publications at PubMed.