Here, we designed a model system using cell lines derived from NSCLC tumors, which are resistant to DM4 or an in-house developed analog of SAR408701, and our anti-CEACAM5 CAR-T cells showed CEACAM5-specific anti-tumor activities for DM4-resistant NSCLCs in vitro and in vivo. This evidence concerns the gene CEACAM5 and neoplasm.