Pooled screening for CAR function identifies novel IL13Rα2-targeted CARs for treatment of glioblastoma

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor (CAR) T-cell therapies are highly effective against B-cell malignancies but have limited success in solid tumors.
• Glioblastoma, a challenging brain tumor, expresses the IL13Rα2 antigen, making it a target for novel therapies.

Approach:

• A pooled screening platform, CARPOOL, was used to generate and select 1.3×10^6 third-generation CARs targeting IL13Rα2 in primary human T cells.
• Selections focused on key anti-tumor functions: cytotoxicity, proliferation, memory formation, and persistence after repeated antigen exposure.

Key Points:

• Each selected CAR demonstrated the desired functional phenotype.
• One CAR exhibited potent cytotoxicity and long-term proliferation against glioblastoma cells in vitro.
• This CAR showed enhanced persistence and effective tumor control in both in vitro and in vivo glioblastoma models.

Conclusions:

• The CARPOOL platform is effective for discovering CARs targeting solid tumors beyond hematological malignancies.
• This study represents the largest exploration of CAR signaling combinations in human primary cells to date.
• The identified CARs hold potential for treating glioblastoma and other IL13Rα2-expressing solid tumors.