title: Phase I Escalating-Dose Trial of CAR-T Therapy Targeting CEA+Metastatic Colorectal Cancers.
abstract: Chimeric antigen receptor T (CAR-T) cells have shown promising efficacy in treatment of hematological malignancies, but its applications in solid tumors need further exploration. In this study, we investigated CAR-T therapy targeting carcino-embryonic antigen (CEA)-positive colorectal cancer (CRC) patients with metastases to evaluate its safety and efficacy. Five escalating dose levels (DLs) (1 × 105to 1 × 108/CAR+/kg cells) of CAR-T were applied in 10 CRC patients. Our data showed that severe adverse events related to CAR-T therapy were not observed. Of the 10 patients, 7 patients who experienced progressive disease (PD) in previous treatments had stable disease after CAR-T therapy. Two patients remained with stable disease for more than 30 weeks, and two patients showed tumor shrinkage by positron emission tomography (PET)/computed tomography (CT) and MRI analysis, respectively. Decline of serum CEA level was apparent in most patients even in long-term observation. Furthermore, we observed persistence of CAR-T cells in peripheral blood of patients receiving high doses of CAR-T therapy. Importantly, we observed CAR-T cell proliferation especially in patients after a second CAR-T therapy. Taken together, we demonstrated that CEA CAR-T cell therapy was well tolerated in CEA+CRC patients even in high doses, and some efficacy was observed in most of the treated patients.
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Wang
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Li
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhouxing
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qianzhen
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Qin
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.affiliation: Department of Oncology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xianquan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Bie
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: lianghoujie@sina.com.
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
authors.affiliation: Medical Clinic of Hematology, Oncology and Tumor Immunology, CCM, Charité-University Medicine Berlin, 10117 Berlin, Germany. Electronic address: gabriele.pecher@charite.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pecher
authors.affiliation: Center of Biotherapy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: cqian8634@gmail.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D000368:Aged; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015870:Gene Expression; D006801:Humans; D016219:Immunotherapy, Adoptive; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D050506:Mutant Chimeric Proteins / Q000235:genetics / Q000276:immunology; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015202:Protein Engineering; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation
chemical_list: D002272:Carcinoembryonic Antigen; D050506:Mutant Chimeric Proteins; D011948:Receptors, Antigen, T-Cell
keywords: CAR-T; CEA; colorectal carcinoma; dose escalating; phase I; safety and efficacy