CAR-T Targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR for Immunotherapy of Lung Cancer: Phase I Clinical Trial

The third generation of CAR-T cells that target GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR have been constructed respectively and their anti-cancer function has been verified by multiple in vitro and in vivo studies.Clinical studies will be performed to test the anti-cancer function of the these individual or combination of the CAR-T cells for immunotherapy of human cancer patients with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR
-CAR-T cell immunotherapy on human cancers will firstly be tested.

开始日期2017-07-01

申办/合作机构

广州医科大学附属第二医院

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项与 PSMA-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的文献（医药）

2024-10-01·Clinical Cancer Research

Redirecting B7-H3.CAR T Cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models

Article

作者: Nguyen, Phuong ; Fleming, Andrew ; Ross, Aaron B. ; Chockley, Peter J. ; Beckett, Alexandra ; Talbot, Lindsay J. ; Wang, Jian ; Gottschalk, Stephen ; Shepphard, Heather ; Chabot, Ashley ; DeRenzo, Christopher

AbstractPurpose:Clinical efficacy of chimeric antigen receptor (CAR) T cells against pediatric osteosarcoma (OS) has been limited. One strategy to improve efficacy may be to drive chemokine-mediated homing of CAR T cells to tumors. We sought to determine the primary chemokines secreted by OS and evaluate the efficacy of B7-H3.CAR T cells expressing the cognate receptors.Experimental Design:We developed a pipeline to identify chemokines secreted by OS by correlating RNA-seq data with chemokine protein detected in media from fresh surgical specimens. We identified CXCR2 and CXCR6 as promising receptors for enhancing CAR T-cell homing against OS. We evaluated the homing kinetics and efficiency of CXCR2- and CXCR6.T cells and homing, cytokine production, and antitumor activity of CXCR2- and CXCR6.B7-H3.CAR T cells in vitro and in vivo.Results:T cells transgenically expressing CXCR2 or CXCR6 exhibited ligand-specific enhanced migration over T cells modified with nonfunctional control receptors. Differential homing kinetics were observed, with CXCR2.T-cell homing quickly and plateauing early, whereas CXCR6.T cells took longer to home but achieved a similar plateau. When expressed in B7-H3.CAR T cells, CXCR2- and CXCR6 modification conferred enhanced homing toward OS in vitro and in vivo. CXCR2- and CXCR6-B7-H3.CAR-treated mice experienced prolonged survival in a metastatic model compared with B7-H3.CAR T-cell-treated mice.Conclusions:Our patient-based pipeline identified targets for chemokine receptor modification of CAR T cells targeting OS. CXCR2 and CXCR6 expression enhanced the homing and anti-OS activity of B7-H3.CAR T cells. These findings support clinical evaluation of CXCR-modified CAR T cells to improve adoptive cell therapy for patients with OS.

2024-09-12·Blood

Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies

Article

作者: Dey, Aonkon ; Cook, Daniella T. ; Wiggin, Hadley R. ; Berger, Trisha R. ; Horick, Nora K. ; Elder, Eva L. ; Schmidts, Andrea ; Leick, Mark B. ; Graham, Charlotte E. ; Katsis, Katelin ; Daley, Heather ; Ritz, Jerome ; Armant, Myriam ; Nikiforow, Sarah ; Lee, Won-Ho ; DiPersio, John F. ; Dolaher, Maria A. ; Nardi, Valentina ; Gallagher, Kathleen M. E. ; Preffer, Fred ; Wehrli, Marc ; Frigault, Matthew J. ; Scarfò, Irene ; Chen, Yi-Bin ; El-Jawahri, Areej ; Huang, Lu ; Bouffard, Amanda ; Maus, Marcela V. ; Parker, Aiyana L. ; Ritchey, Julie ; Haradhvala, Nicholas J. ; Chekmasova, Alena A.

AbstractWe report a first-in-human clinical trial using chimeric antigen receptor (CAR) T cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies. Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T cells. CAR-37 T cells expanded in the peripheral blood of all patients and, at peak, comprised >94% of the total lymphocytes in 4 of 5 patients. Tumor responses were observed in 4 of 5 patients with 3 complete responses, 1 mixed response, and 1 patient whose disease progressed rapidly and with relative loss of CD37 expression. Three patients experienced prolonged and severe pancytopenia, and in 2 of these patients, efforts to ablate CAR-37 T cells, which were engineered to coexpress truncated epidermal growth factor receptor, with cetuximab were unsuccessful. Hematopoiesis was restored in these 2 patients after allogeneic hematopoietic stem cell transplantation. No other severe, nonhematopoietic toxicities occurred. We investigated the mechanisms of profound pancytopenia and did not observe activation of CAR-37 T cells in response to hematopoietic stem cells in vitro or hematotoxicity in humanized models. Patients with pancytopenia had sustained high levels of interleukin-18 (IL-18) with low levels of IL-18 binding protein in their peripheral blood. IL-18 levels were significantly higher in CAR-37–treated patients than in both cytopenic and noncytopenic cohorts of CAR-19–treated patients. In conclusion, CAR-37 T cells exhibited antitumor activity, with significant CAR expansion and cytokine production. CAR-37 T cells may be an effective therapy in hematologic malignancies as a bridge to hematopoietic stem cell transplant. This trial was registered at www.ClinicalTrials.gov as #NCT04136275.

100 项与 PSMA-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的药物交易

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