Research progress of CAR-T therapy for lung cancer

CAR-T is the abbreviation of Chimeric Antigen Receptor T Cell Therapy, and it is a new type of tumor immunotherapy

 In 2017, the US FDA approved the first CD19-targeted immune cell therapy-CAR-T (CTL019, Kymriah), and officially launched it, opening a new frontier of medical innovation

At present, CAR-T therapy is relatively successful in the research of hematological malignancies, but the successful research in solid tumors (such as lung cancer) is still very limited

Research progress of CAR-T in non-small cell lung cancer (NSCLC)

Current research status of targeting antigen EGFR

EGFR is a common driver gene for non-small cell lung cancer, which is related to tumor proliferation, angiogenesis and metastasis

Beijing 301 Hospital took the lead in carrying out CAR-T treatment in China, and the effect was remarkable

 In a phase I clinical trial conducted by Sun Yat-Sen University, the effectiveness and safety of CXC chemokine receptor (CXCR) type 5 modified anti-EGFR CAR-T cells in the treatment of EGFR-positive patients with advanced non-small cell lung cancer are being evaluated (NCT04153799)

 Current status of research on targeted antigen CEA

CEA is a common tumor marker for gastrointestinal tumors

 Research progress of targeting PD-L1

In recent years, PD-1 antibody has achieved satisfactory results in in vitro cell co-culture models, in vivo animal models, and clinical trials for the treatment of various cancers including non-small cell lung cancer, and its clinical application is also increasing.

 In the clinical stage, a phase I early study (NCT03060343) used autologous CAR-T cells targeting PD-L1 and CD80/CD86 to treat relapsed or refractory non-small cell lung cancer to determine safety, tolerability, and transplantation.

Other targeted antigens 

NSCLC is the most common targeting CAR-T antigens include EGFR, CEA, PD-L1, CD80 / CD86 and the like

Research progress of CAR-T in small cell lung cancer (SCLC)

 Previous literature reports that about 80% of small cell lung cancer (SCLC) patients have positive expression of DLL3 in tumor tissues, but almost no expression in normal tissues

 Research on AMG 119 targeted therapy for SCLC is ongoing

 In addition, there is a phase I trial of AMG 757 in the treatment of SCLC, which also targets DLL3

In terms of safety, the incidence of treatment-related adverse events (TRAE)≥3 was 23%, the incidence of common TRAE cytokine release syndrome (CRS) was 44%, and the incidence of ≥3 CRS was 2%

CAR-T cell therapy, as a new strategy for the treatment of lung cancer, has made considerable progress, and related clinical studies are also in progress