Clinical Trials

Overview

About this study

The chimeric antigen receptor (CAR) T-cell therapy is a revolutionary cellular immunotherapy strategy that has transformed the treatment of B cell malignancies by engineering T cells to recognize B cell specific tumor markers; however, attempts to treat solid tumors with CAR T-cells have identified unique challenges that have rendered CAR T cells less effective against these tumors. Conventional CARs are designed to target tumor-associated antigens, but antigenic heterogeneity and the variable nature of surface antigen expression provide escape mechanisms for solid tumors from CAR T-cell attack. [1, 2] The solid tumor stroma acts as an immunosuppressive cloud that impedes the homing of peripheral CAR T-cells into the tumor microenvironment (TME). The hostile TME can also drive CAR T-cells to functional exhaustion and metabolic dysfunction, thus blunting the therapeutic efficacy of CAR T-cells.[3] Oncolytic viruses or radiation that generate local inflammation in the TME have been shown to promote T cell homing and infiltration [4] but do not address the exhaustion of tumor infiltrating lymphocytes (TILs). The PD-1/PD-L1 cascade allows tumors to evade the immune system by suppressing T cell function within the TME. [5, 6] An ideal adoptive cellular therapy must possess the ability to not only return to the site of the tumor but must also retain cytotoxic potential after a recognition event. We present here a CAR design that allows PD-1 to recognize PD-L1 on the tumor; however, the intracellular CAR design is one that results in T cell activation as opposed to inhibition. We hypothesize that targeting melanoma with a PD-1 (MC9324) CAR TIL therapy would capitalize on the tumor homing machinery of the TIL to drive the CAR TIL to the tumor where engagement of the PD-1 domain of the CAR with PD-L1 on the tumor cell would result in T cell cytotoxic killing.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Participating Mayo Clinic locations

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