Novel PAP-targeted CAR-T therapy enhances antitumor efficacy through CoupledCAR approach

Area of Science:

• Oncology
• Immunotherapy
• Cancer Biology

Background:

• Solid tumor treatment with CAR-T cells faces challenges due to limited tumor-specific targets and poor CAR-T cell expansion/function.
• Current CAR-T therapies for prostate cancer lack specificity, increasing safety risks.
• Prostate cancer is a significant global health concern, necessitating improved therapeutic strategies.

Purpose of the Study:

• To identify a specific target for prostate cancer CAR-T therapy.
• To develop a novel CAR-T cell expansion platform for solid tumors.
• To evaluate the efficacy and mechanism of the new therapeutic approach.

Main Methods:

• Analyzed PAP expression in prostate cancer using The Cancer Genome Atlas and immunohistochemistry.
• Generated and selected PAP-specific antibodies from a human single-chain antibody library.
• Constructed PAP-targeted CAR-T cells and evaluated antitumor efficacy in vitro and in vivo, including scRNA-Seq analysis.

Main Results:

• PAP is specifically expressed in prostate cancer cells, not in other tissues.
• PAP CAR-T cells demonstrated significant antitumor efficacy both in vitro and in vivo.
• The CoupledCAR system effectively expanded PAP CAR-T cells, promoting a memory-like state and enhancing antitumor activity via costimulatory and cytokine signals.

Conclusions:

• Prostatic acid phosphatase (PAP) is a validated, specific target for CAR-T therapy in prostate cancer.
• The CoupledCAR platform technology enables antigen-independent expansion of tumor-targeting CAR-T cells.
• This approach enhances CAR-T cell functionality against solid tumors, offering a promising new therapeutic strategy.