Enhancing adoptive T cell therapy with synergistic host immune engagement promotes long-term protection against solid tumors

Adu-Berchie, K.; Brockman, J. M.; Liu, Y.; Zhang, D. K. Y.; Najibi, A. J.; Stafford, A.; Sobral, M. C.; Binenbaum, Y.; Dellacherie, M. O.; Mooney, D. J.

doi:10.1101/2022.09.10.507437

bioRxiv · 10.1101/2022.09.10.507437

Enhancing adoptive T cell therapy with synergistic host immune engagement promotes long-term protection against solid tumors

Adu-Berchie, K.·Brockman, J. M.·Liu, Y.·Zhang, D. K. Y.·Najibi, A. J.·Stafford, A.·Sobral, M. C.·Binenbaum, Y.·Dellacherie, M. O.·Mooney, D. J.

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Abstract

Adoptive T cell therapy provides the T cell pool needed for immediate tumor debulking, but the infused T cells generally have a narrow repertoire for antigen recognition and limited ability for long-term protection. Here, we present a biomaterial platform that enhances adoptive T cell therapy by synergistically engaging the host immune system via in-situ antigen-free vaccination. T cells alone loaded into these localized cell depots provided significantly better control of subcutaneous B16-F10 tumors than T cells delivered through direct peritumoral injection or intravenous infusion. The anti-tumor response was significantly enhanced when T cell delivery was combined with biomaterial-driven accumulation and activation of host immune cells, as this prolonged the activation state of the delivered T cells, minimized host T cell exhaustion, and enabled long-term tumor control. This integrated approach provides both immediate tumor debulking and long-term protection against solid tumors, including against tumor antigen escape.

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Adu-Berchie, K., Brockman, J. M., Liu, Y., Zhang, D. K. Y., Najibi, A. J., Stafford, A., Sobral, M. C., Binenbaum, Y., Dellacherie, M. O., Mooney, D. J.. 2022-09-13. Enhancing adoptive T cell therapy with synergistic host immune engagement promotes long-term protection against solid tumors. https://doi.org/10.1101/2022.09.10.507437

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