Coexpression of c-Jun in multiple-chain DAP-CAR-engineered T-cells for solid tumor therapy

Area of Science:

• Immunology
• Cancer Biology
• Cell Therapy

Background:

• Chimeric antigen receptor T-cell (CAR-T) therapy shows promise for cancer treatment.
• Enhancing CAR-T cell persistence and efficacy is crucial for improving clinical outcomes.
• Mesothelin (MSLN) is a target antigen for certain solid tumors.

Purpose of the Study:

• To investigate the impact of c-Jun overexpression on the persistence and antitumor efficacy of DAP-CAR-T cells targeting MSLN.
• To evaluate the effects of c-Jun on CAR-T cell expansion, cytokine secretion, and T-cell phenotypes.

Main Methods:

• In vitro and in vivo studies using MSLN-targeting DAP-CAR-T cells.
• ELISA and real-time cell analysis for in vitro assessments.
• Xenograft models were used for in vivo evaluation of antitumor effects.

Main Results:

• c-Jun overexpression did not alter DAP-CAR-T cell expansion but slightly increased IL-2 secretion.
• Antitumor efficacy in vitro and in vivo was not improved by c-Jun.
• c-Jun reduced LAG3 expression and increased the ratio of central memory (Tcm) and naive/stem Tscm cells in vivo.

Conclusions:

• Coexpression of c-Jun in DAP-CAR-T cells slightly enhances T-cell exhaustion reduction and central memory phenotype maintenance.
• These findings suggest a potential role for c-Jun in improving DAP-CAR-T cell therapy for solid tumors.