title: 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.
abstract: 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 (scFv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin (IL) 12 (named SM3-CAR). The other CAR-T cell line carried the SM3 scFv sequence modified to improve its binding to MUC1 antigen (named pSM3-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 pSM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.
authors.affiliation: The Cyrus Tang Hematology Center; Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, China.|Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Fengtao
authors.initials: F
authors.lastname: You
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Licui
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Bozhen
authors.initials: B
authors.lastname: Zhang
authors.affiliation: West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.affiliation: West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Liao
authors.affiliation: West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Cardiothoracic Surgery, Chinese People's Armed Police Force of Zhejiang Corps Hospital, Jiaxing, 314000, China.
authors.forename: Kaiqi
authors.initials: K
authors.lastname: Du
authors.affiliation: Department of Cardiothoracic Surgery, Chinese People's Armed Police Force of Zhejiang Corps Hospital, Jiaxing, 314000, China.
authors.forename: Youcai
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Cyrus Tang Hematology Center; Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Meng
authors.affiliation: The Medical Group of Zhengzhou First People's Hospital, Zhengzhou, 450004, China.
authors.forename: Zhishu
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Zong
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Man
authors.initials: M
authors.lastname: Lu
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Jirong
authors.initials: J
authors.lastname: Tang
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Yafen
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Pharmacy, Xi'an Jiaotong University, Suzhou, 215123, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Zhai
authors.affiliation: College of Pharmacy, Xi'an Jiaotong University, Suzhou, 215123, China.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Wang
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Sisi
authors.initials: S
authors.lastname: Ye
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Qi
authors.affiliation: The Cyrus Tang Hematology Center; Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, China. yanglin@suda.edu.cn.|Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, 215123, China. yanglin@suda.edu.cn.|Persongen Biomedicine (Suzhou) Co., Ltd, Suzhou, 215123, China. yanglin@suda.edu.cn.|College of Pharmacy, Xi'an Jiaotong University, Suzhou, 215123, China. yanglin@suda.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005834:Genital Neoplasms, Male / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D057809:HEK293 Cells; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D061986:MCF-7 Cells; D008297:Male; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012669:Seminal Vesicles / Q000473:pathology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D016896:Treatment Outcome
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies
keywords: CAR-T therapy; MUC1; seminal vesicle cancer; solid tumor