This is a study in which pancreatic cancer patients receive a immunotherapy with CART-meso cells administered at 3 days after one dose of cyclophosphamide. CART-meso cells are patients' own T cells lentivirally transduced to express anti-mesothelin scFv fused to TCRζ and 4-1BB costimulatory domains.The lymphodepletion with cyclophosphamide may prolong the persistence of CART cells.

开始日期2018-07-11

申办/合作机构

深圳宾德生物技术有限公司

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100 项与 Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.) 相关的临床结果

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100 项与 Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.) 相关的转化医学

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100 项与 Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.) 相关的专利（医药）

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项与 Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.) 相关的文献（医药）

2023-05-01·Bone Marrow Transplantation

SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination

Article

作者: Gago, Beatriz ; Villalon, Lucia ; Villalba, Marta ; Conesa-Garcia, Venancio ; Martino, Rodrigo ; Chorão, Pedro ; García-Cadenas, Irene ; Ferrer, Elena ; Sureda, Anna ; Cabero, Almudena ; López-Corral, Lucia ; Teruel, Anabel ; Olave, María T ; Avendaño-Pita, Alejandro ; Hernández-Rivas, José Ángel ; Terol, María-José ; Sánchez-Salinas, Andrés ; Sanz-Linares, Gabriela ; Tormo, Mar ; Solano, Carlos ; Arroyo, Ignacio ; Garcia-Gutierrez, Valentín ; Piñana, José Luis ; Vazquez, Lourdes ; Navarro, David ; Pérez, Ariadna ; Pascual, María-Jesús ; Cedillo, Ángel

The kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] (p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.

2021-03-15·Aging3区 · 医学

APDL1-CART cells exhibit strong PD-L1-specific activity against leukemia cells

3区 · 医学

Article

作者: Peng, Qunyi ; Zheng, Yan ; Zhu, Xiongpeng ; Liu, Shengquan ; Xin, Pengliang ; Li, Chuntuan

Chimeric antigen receptor (CAR) T cells target specific tumor antigens and lyse tumor cells in an MHC-independent manner. However, the efficacy of CAR-T cell and other cancer immunotherapies is limited by the expression of immune-checkpoint molecules such as programmed death-ligand 1 (PD-L1) on tumor cells, which binds to PD-1 receptors on T cells leading to T cell inactivation and immune escape. Here, we incorporated a PD-L1-targeted single-chain variable fragment (scFv) fusion protein sequence into a CAR vector to generate human anti-PD-L1-CAR-T cells (aPDL1-CART cells) targeting the PD-L1 antigen. Unlike control T cells, aPDL1-CART cells significantly halted the expansion and reduced the viability of co-cultured leukemia cells (Raji, CD46, and K562) overexpressing PD-L1, and this effect was paralleled by increased secretion of IL-2 and IFN-γ. The antitumor efficacy of aPDL1-CART cells was also evaluated in vivo by co-injecting control T cells or aPDL1-CART cells along with PDL1-CA46 cells to generate subcutaneous xenografts in NCG mice. Whereas large tumors developed in mice inoculated with PDL1-CA46 cells alone or together with control T cells, no tumor formation was detected in xenografts containing aPDL1-CART cells. Our data suggest that immune checkpoint-targeted CAR-T cells may be useful for controlling and eradicating immune-refractory hematological malignancies.

2019-11-01·Molecular Therapy1区 · 医学

Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers

1区 · 医学

Article

作者: Lacey, Simon F ; O'Hara, Mark H ; Nelson, Anne Marie ; Plesa, Gabriela ; Melenhorst, J Joseph ; Moon, Edmund ; Tian, Lifeng ; Soulen, Michael C ; Tanyi, Janos L ; McGarvey, Maureen ; Haas, Andrew R ; Farabaugh, Caitlin S ; June, Carl H ; Beatty, Gregory L ; Torigian, Drew A ; Gladney, Whitney L ; Levine, Bruce L ; Albelda, Steven M

This phase I study investigated the safety and activity of lentiviral-transduced chimeric antigen receptor (CAR)-modified autologous T cells redirected against mesothelin (CART-meso) in patients with malignant pleural mesothelioma, ovarian carcinoma, and pancreatic ductal adenocarcinoma. Fifteen patients with chemotherapy-refractory cancer (n = 5 per indication) were treated with a single CART-meso cell infusion. CART-meso cells were engineered by lentiviral transduction with a construct composed of the anti-mesothelin single-chain variable fragment derived from the mouse monoclonal antibody SS1 fused to intracellular signaling domains of 4-1BB and CD3zeta. Patients received 1-3 × 10⁷ or 1-3 × 10⁸ CART-meso cells/m² with or without 1.5 g/m² cyclophosphamide. Lentiviral-transduced CART-meso cells were well tolerated; one dose-limiting toxicity (grade 4, sepsis) occurred at 1-3 × 10⁷/m² CART-meso without cyclophosphamide. The best overall response was stable disease (11/15 patients). CART-meso cells expanded in the blood and reached peak levels by days 6-14 but persisted transiently. Cyclophosphamide pre-treatment enhanced CART-meso expansion but did not improve persistence beyond 28 days. CART-meso DNA was detected in 7/10 tumor biopsies. Human anti-chimeric antibodies (HACA) were detected in the blood of 8/14 patients. CART-meso cells were well tolerated and expanded in the blood of all patients but showed limited clinical activity. Studies evaluating a fully human anti-mesothelin CAR are ongoing.

100 项与 Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
胰腺继发性恶性肿瘤	临床3期	中国	深圳宾德生物技术有限公司	2018-07-11
胰腺癌	临床2期	中国	南京医科大学第一附属医院	-
胰腺癌	临床2期	中国	深圳宾德生物技术有限公司	-
胃癌	临床2期	中国	南京医科大学第一附属医院	-
胃癌	临床2期	中国	深圳宾德生物技术有限公司	-