Enterotoxins can support CAR T cells against solid tumors.

Area of Science:

• Immunology
• Cancer Therapy
• Cellular Engineering

Background:

• Solid tumors often show minimal response to CAR T cell therapy due to immunosuppression.
• CAR T cells struggle with sustained activation and proliferation within the tumor microenvironment.

Purpose of the Study:

• To investigate if promoting CAR T cell and APC interaction in lymphoid tissue enhances anti-tumor responses.
• To explore strategies for improving CAR T cell efficacy in solid tumors.

Main Methods:

• Combined CAR T cell transfer with staphylococcal enterotoxin-B (SEB) to link T cells and APCs.
• Utilized a bispecific antibody targeting CAR T cells and CD40.
• Administered FTY720 to inhibit lymphocyte egress from lymph nodes.

Main Results:

• SEB significantly enhanced CAR T cell proliferation and function.
• Combination therapy with SEB increased solid tumor growth inhibition in mice.
• CAR T cell expansion occurred in lymphoid tissue, and inhibiting egress abrogated SEB's benefit.
• Bispecific antibody also enhanced CAR T cell activity and anti-tumor effects.

Conclusions:

• Facilitating CAR T cell and APC interaction is a viable strategy to improve anti-tumor activity.
• This approach can overcome limitations posed by the immunosuppressive tumor microenvironment.
• Model systems demonstrate proof-of-principle for enhancing CAR T cell therapy.