This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to target mesothelin and express PD-1 antibodies in adult patients with advanced recurrent or refractory malignant solid tumors, which were positive expression of mesothelin.

Start Date06 Aug 2018

Sponsor / Collaborator

Shanghai Cell Therapy Research Institute

ChiCTR2000036445 / RecruitingPhase 1/2IIT

A Clinical Study of CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for Patients With MUC1 Positive Advanced Solid Tumors

Start Date30 Apr 2018

Sponsor / Collaborator

Shanghai No. 10 People's Hospital

100 Clinical Results associated with PD-1 antibody expressing mesoCAR-T cells(Shanghai Cell Therapy Research Institute)

100 Translational Medicine associated with PD-1 antibody expressing mesoCAR-T cells(Shanghai Cell Therapy Research Institute)

100 Patents (Medical) associated with PD-1 antibody expressing mesoCAR-T cells(Shanghai Cell Therapy Research Institute)

Literatures (Medical) associated with PD-1 antibody expressing mesoCAR-T cells(Shanghai Cell Therapy Research Institute)

01 Nov 2022·Cancer Genetics

Mesothelin CAR‐T cells secreting PD‐L1 blocking scFv for pancreatic cancer treatment

Article

Author: Yan, Zhiqiang ; Wang, Yiting ; Yu, Lei ; Wang, Jing ; Ye, Jing ; Zhao, Shimin ; Li, Minghao ; Wang, Yeying ; Fang, Xiaoyan

PD-1/PD-L1 pathway caused immunosuppression accounts, at least partly, for the poor therapeutic effect of Chimeric Antigen Receptor T (CAR-T) on solid tumors. In this study, we designed and prepared CAR-T cells that could secrete PD-L1 blocking antibody and target Mesothelin antigen (Sec-MesoCAR-T), to remove the immunosuppressive effect of tumor on CAR-T cells, thereby increasing the therapeutic effect of CAR-T cells on pancreatic cancer. The CAR-T cells that could not secret PD-L1 blocking antibodies (MesoCAR-T) were used as a control. Sec-MesoCAR-T cells showed an enhanced inhibitory effect on BxPC-3 tumor than MesoCAR-T cells in vitro and in vivo. Besides, Sec-MesoCAR-T cells secreted higher level of cytokines including IL-2, IL-6 and IFN-γ in vitro than MesoCAR-T cells. Following injection, there were significantly more CAR-T cells in the peripheral blood of Sec-MesoCAR-T group than that of MesoCAR-T group. This work demonstrated that the PD-L1 antibody secreted by Sec-MesoCAR-T cells relieved the immunosuppressive effect of pancreatic cancer on CAR-T cells and improved the anti-tumor activity of CAR-T cells, which has a good guiding significance for the clinical application of CAR-T cells in treating solid tumors.

100 Deals associated with PD-1 antibody expressing mesoCAR-T cells(Shanghai Cell Therapy Research Institute)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Mesothelin positive Solid Tumors	Phase 2	CN	Shanghai Cell Therapy Research Institute	06 Aug 2018
Advanced Malignant Solid Neoplasm	Discovery	CN	Shanghai Cell Therapy Research Institute	06 Aug 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2022 Manual	Phase 1	Advanced cancer Third line	7	αPD-1-mesoCAR-T cells	(ctsennjmhu) = emsysoljmd ndacfuutdx (fnsjbzarja ) View more	Positive	02 Jun 2022
NCT03615313 (ASCO2020) Manual	Phase 1	Relapsed Solid Neoplasm	10	aPD1-MSLN-CAR T cells	(chdpqbpepd) = vbmqqftlbt sjewfhmpdh (gijqtmyzvx, 13 - 180) View more	Positive	29 May 2020

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PD-1 antibody expressing mesoCAR-T cells(Shanghai Cell Therapy Research Institute)

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