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.
Show 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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