Interleukin-23 engineering improves CAR T cell function in solid tumors.

Area of Science:

• Immunology
• Cancer Biology
• Cell Therapy

Background:

• Chimeric antigen receptor (CAR) T cell therapy shows promise for cancer treatment.
• Cytokines like IL-15 can enhance CAR T cell activity but may cause toxicity.
• Interleukin-23 (IL-23) is a cytokine that promotes T cell proliferation.

Purpose of the Study:

• To engineer T cells for selective proliferation via autocrine IL-23 signaling.
• To evaluate the efficacy and safety of engineered p40-Td CAR T cells against solid tumors.

Main Methods:

• T cells were engineered to express the IL-23 p40 subunit (p40-Td cells).
• TCR stimulation was used to induce IL-23 receptor and p19 subunit expression.
• In vitro and in vivo (xenograft and syngeneic mouse models) studies compared p40-Td CAR T cells with conventional CAR T cells.

Main Results:

• p40-Td CAR T cells exhibited enhanced in vitro antitumor capacity, with increased granzyme B and decreased PD-1 expression.
• In vivo studies showed superior efficacy of p40-Td CAR T cells in solid tumor models.
• Engineered CAR T cells demonstrated attenuated side effects compared to those expressing IL-18 or IL-15.

Conclusions:

• Autocrine IL-23 signaling via engineered p40-Td CAR T cells enhances antitumor efficacy.
• This approach offers a potentially safer and more effective CAR T cell therapy strategy.
• p40-Td CAR T cells represent a promising advancement in adoptive cell therapy for cancer.