Parallel 4-1BB Signaling in Dual DLL3/CD56-Targeting CAR T Cells Triggers Adaptive Proliferation and Functional Persistence to Eradicate Small Cell Lung Cancer.

Parallel 4-1BB signaling in DLL3/CD56-targeting CAR T cells enhances persistence and antitumor activity in small cell lung cancer models.

• Why it matters: Solid tumors like small cell lung cancer often resist CAR T-cell therapy due to limited intratumoral persistence and poor proliferation, hindering treatment success.
• What they did: Researchers engineered CAR T cells with parallel 4-1BB signaling (DBBζ.CBB) and a CD56 chimeric switch receptor, testing their effects in preclinical SCLC models through tumor infiltration, persistence, and activity assessments.
• The result: DBBζ.CBB cells showed sustained tumor infiltration, prolonged persistence, and superior antitumor effects, with mechanistic insights revealing enhanced early expansion, memory maintenance, and delayed exhaustion, which together support durable responses.