Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells

Recent progress in chimeric antigen receptor-modified T-cell(CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment(sc Fv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin(IL) 12(named SM3-CAR). The other CAR-T cell line carried the SM3 sc Fv sequence modified to improve its binding to MUC1 antigen(named p SM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1+ seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that p SM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.

High-throughput sequencing detection and ensartinib treatment of lung cancer harboring NTRK1 fusion

Dear Editor,Although fusion events involving neurotrophic receptor tyrosine kinase 1,2,and 3 genes(NTRK1,NTRK2,and NTRK3,encoding TRKA/B/C respectively)were found in diverse tumor types,only 0.1%-0.3%of lung cancer patients harbor an NTRK(and mostly NTRK1)fusion as the primary oncogenic event[1].Such low prevalence may be partially due to the limited availability of first-line assays for detecting rare fusion events[2].Immunohistochemistry is limited by sensitivity and variable tissue background,and fluorescence in-situ hybridization falls short of elucidating functional significance such as the identity of the partner or structure of the transcript.While DNA next-generation sequencing(NGS)is suitable for mutation calling(single nucleotide variation[SNV]and insertion-or-deletion[indel]),and RNA NGS is particularly effective in detecting fusions[3],routinely performing these two assays together is labor-intensive.As a solution,we have developed a single NGS assay(PANO-Seq)for unified RNA/DNA target enrichment library preparation[4],which takes about 12 hours and $10 to prepare.