Biogenic Selenium Nanoparticles Potentiate Anti-Mesothelin CAR-T Cell Therapy in a Syngeneic TNBC Model.

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Triple-negative breast cancer (TNBC) is an aggressive cancer subtype with limited targeted treatment options.
• Chimeric antigen receptor (CAR)-T cell therapy shows promise but faces challenges in solid tumors due to the immunosuppressive tumor microenvironment (TME).

Purpose of the Study:

• To generate anti-mesothelin CAR-T cells and assess their efficacy against TNBC in a preclinical model.
• To investigate the potential of biogenic selenium nanoparticles (bSeNPs) to enhance CAR-T cell therapy by modulating the TME.

Main Methods:

• Generated anti-mesothelin CAR-T cells and tested their in vitro activity against 4T1 TNBC cells.
• Administered CAR-T cells alone or in combination with bSeNPs intratumorally in mice with 4T1 TNBC tumors.
• Assessed tumor growth, histopathology, and gene expression of immunosuppressive and apoptotic markers.

Main Results:

• Anti-mesothelin CAR-T cells exhibited potent in vitro cytotoxicity, proliferation, and cytokine production against TNBC cells.
• Both CAR-T monotherapy and combination therapy significantly reduced tumor growth compared to controls.
• Combination therapy demonstrated a trend toward improved tumor control, reduced tumor cell proliferation and angiogenesis, and modulated TME by decreasing PD-L1, TGF-β1, IL-10, and enhancing pro-apoptotic signaling.

Conclusions:

• Anti-mesothelin CAR-T cells hold therapeutic potential for TNBC.
• Biogenic selenium nanoparticles (bSeNPs) may enhance CAR-T cell efficacy in solid tumors by modulating the TME.
• Further research into nanoparticle-assisted CAR-T cell strategies is warranted for solid tumor treatment.