Novel personalized cancer vaccine platform based on Bacillus Calmette-Guerin

Ylosmaki, E.; Martins, B.; Fusciello, M.; Feola, S.; Hamdan, F.; Chiaro, J.; Ylosmaki, L.; Vaughan, M. J.; Viitala, T.; Kulkarni, P. S.; Cerullo, V.

doi:10.1101/2021.03.05.434062

bioRxiv · 10.1101/2021.03.05.434062

Novel personalized cancer vaccine platform based on Bacillus Calmette-Guerin

Ylosmaki, E.·Martins, B.·Fusciello, M.·Feola, S.·Hamdan, F.·Chiaro, J.·Ylosmaki, L.·Vaughan, M. J.·Viitala, T.·Kulkarni, P. S.·Cerullo, V.

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Abstract

Intratumoural bacillus Calmette-Guerin (BCG) therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumour. Here, we have developed a novel cancer vaccine platform based on BCG that can direct BCG-induced immune responses against tumour antigens. By physically attaching tumour-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoural T cell-specific immune responses towards the attached tumour antigens. These therapeutic peptides can be attached to the mycobacterial outer membrane using a cell-penetrating peptide sequence derived from human immunodeficiency virus Tat, N-terminally fused to the tumour-specific peptides. Alternatively, therapeutic peptides can be conjugated with a poly-lysine sequence N-terminally fused to the tumour-specific peptides. Using two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the anti-tumour responses of BCG can be significantly improved by coating the BCG with tumour-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-PD-1 immune checkpoint inhibitor therapy, the number of responders to anti-PD-1 immunotherapy can be significantly increased.

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Ylosmaki, E., Martins, B., Fusciello, M., Feola, S., Hamdan, F., Chiaro, J., Ylosmaki, L., Vaughan, M. J., Viitala, T., Kulkarni, P. S., Cerullo, V.. 2021-03-05. Novel personalized cancer vaccine platform based on Bacillus Calmette-Guerin. https://doi.org/10.1101/2021.03.05.434062

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