Tumor relapse prevented by combining adoptive T cell therapy with Salmonella typhimurium

ABSTRACT

We recently reported that therapeutic vaccination with live tumor antigen-producing Salmonella typhimurium rescues dysfunctional endogenous T cell responses and eradicates long-established tumors refractory to αCTLA-4 and αPD-L1 checkpoint inhibitor blockade. Here, we show that live intravenously injected or heat-killed (HK) intratumorally injected Salmonella typhimurium, even when not producing tumor antigen, synergize with adoptive T cell therapy to eradicate tumors. These data demonstrate that the combination of adoptive T cell transfer with the injection of live or dead Salmonella typhimurium is a promising approach for cancer treatment.

KEYWORDS:

• Adoptive T cell therapy
• bacteria
• macrophage
• relapse
• tumor stroma

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

This research was supported by the NIH grants R01-CA37516, R01-CA22677, and P01-CA97296, to H. Schreiber and the Graduate Training in Growth and Development grant T32 HD009007 to DC. Binder. AntiCancer Inc. provided the Salmonella typhimurium A1-R strain.