GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335371/primary200OKTranscriptomics Mus musculusHomo sapiens OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335371GEOGSEfalseCAR-T-drug conjugate against solid tumor [RNA-seq/BCR-seq]Chimeric antigen receptor (CAR)-T cell therapy has been clinically successful in hematologic malignancies but faces challenges in solid tumors, including limited infiltration, immunosuppressive microenvironments and antigen heterogeneity. While combining CAR-T cell therapy with chemotherapy can enhance antitumor activity, this often leads to substantial systemic toxicity. Here we show that CAR-T-drug conjugate (CAR-T-D-C), generated through click chemistry-mediated conjugation of cytotoxic payloads to antigen-specific CAR-T cells, enable localized drug delivery while preserving CAR-T cell function. CAR-T-D-Cs incorporating different CAR-T cell binders exhibit robust antitumor activity across multiple human xenografts and syngeneic tumor models. Spatial transcriptomic analyses reveal enhanced intratumoral CAR-T infiltration and activation following CAR-T-D-C treatment . Compared with conventional CAR-T therapy, CAR-T-D-C enhances immune cell infiltration, augments effector functions, promotes antigen spreading and amplifies systemic anti-tumor immunity. CAR-T-D-C represents a versatile therapeutic platform that combines the specificity of cellular immunotherapy with the potency of small-molecule therapeutics for treatment of solid tumors.2026/06/26GSE335371GSM9816103GSM9812611GSM9812610GSM9812613GSM9812612GSM9812608GSM9812607GSM9812609GSM9812604GSM9812603GSM9812614GSM9812606GSM98126053428116417335371 Mus musculusHomo sapiens