Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Solid tumors feature a complex tumor microenvironment (TME) with soluble factors like TGF-β.
• TGF-β suppresses T cell function and promotes tumor invasiveness.
• Current CAR T cell therapies target cell-surface antigens, necessitating strategies for soluble TME targets.

Purpose of the Study:

• To investigate the use of Adapter CAR (AdCAR) T cells for targeting soluble latent TGF-β in the TME.
• To assess the efficacy of AdCAR T cells in detecting and responding to soluble TGF-β.
• To evaluate combined targeting of soluble TGF-β and tumor-associated antigens (TAAs) using AdCAR T cells.

Main Methods:

• Development and application of AdCAR T cells with specific adapters.
• In vitro and in vivo testing in a pancreatic tumor model.
• Evaluation of AdCAR T cell activation, cytokine production, and tumor cell killing.

Main Results:

• AdCAR T cells successfully detected soluble latent TGF-β in vitro and in vivo.
• Sensing of soluble TGF-β induced AdCAR T cell activation and effector cytokine release.
• Combined targeting of soluble TGF-β and CD66c TAA demonstrated potential for dual therapeutic action.

Conclusions:

• AdCAR T cells offer a novel strategy for targeting soluble latent TGF-β within the TME.
• This approach expands the range of targetable moieties for CAR T cell therapy.
• AdCAR T cells show promise for enhancing anti-tumor immunity by addressing both soluble factors and cellular targets.