TREM1/DAP12 based novel multiple chain CAR‐T cells targeting DLL3 show robust anti‐tumour efficacy for small cell lung cancer

• DOI: 10.1111/imm.13776
• Publication Date: 2024-03-12T08:35:57Z
• Authors: Fengqi Nie; Yuli Chen; Yanming Hu; Peng Huang; Xuefei Shi; Jingsheng Cai; Mantang Qiu; Enxiu Wang; Kaihua Lu; Ming Sun
• Keywords: 0301 basic medicine; Lung Neoplasms; Receptors, Chimeric Antigen; T-Lymphocytes; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Mice, SCID; Small Cell Lung Carcinoma; Immunotherapy, Adoptive; Xenograft Model Antitumor Assays; Triggering Receptor Expressed on Myeloid Cells-1; Mice; 03 medical and health sciences; Cell Line, Tumor; Humans; Animals; Female; Adaptor Proteins, Signal Transducing

Abstract Small cell lung cancer (SCLC), recognized as the most aggressive subtype of cancer, presents an extremely poor prognosis. Currently, patients with small face a significant dearth effective alternative treatment options once they experience recurrence and progression after first‐line therapy. Despite promising efficacy immunotherapy, particularly immune checkpoint inhibitors in non‐small (NSCLC) various other tumours, its impact on significantly enhancing prognosis SCLC remains elusive. DLL3 has emerged compelling target for targeted therapy due to high expression membranes neuroendocrine carcinoma cells, minimal no normal cells. Our previous work led development novel multiple chain chimeric antigen receptor (CAR) leveraging TREM1 DAP12, which efficiently activated T cells conferred potent cytotoxicity. In this study, we have developed DLL3‐TREM1/DAP12 CAR‐T (DLL3‐DT CAR‐T) therapy, demonstrating comparable anti‐tumour against vitro. murine xenograft patient‐derived models, DLL3‐DT exhibited more robust tumour eradication efficiency than second‐generation DLL3‐BBZ Furthermore, observed elevated memory phenotypes, induced durable responses, activation under antigen‐presenting Collectively, these findings suggest that may offer potentially therapeutic strategy treating DLL3‐expressing solid tumours.