Delving into the Latest Updates on Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.) with Synapse

Overview

Basic Info

Drug Type

Autologous CAR-T

Synonyms

CART-meso cells, Mesothelin CAR-T cell therapy

Target

MSLN

Action

inhibitors

Mechanism

MSLN inhibitors(Mesothelin inhibitors), Gene transference, T lymphocyte replacements

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease

Active Indication

Pancreatic CancerStomach Cancer

Inactive Indication

Metastatic Pancreatic Cancer

Originator Organization

Shenzhen Binde Biotechnology Co., Ltd.

Active Organization

Shenzhen Binde Biotechnology Co., Ltd.Jiangsu Provincial People's Hospital

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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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.

Start Date11 Jul 2018

Sponsor / Collaborator

Shenzhen Binde Biotechnology Co., Ltd.

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100 Clinical Results associated with Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.)

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100 Translational Medicine associated with Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.)

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100 Patents (Medical) associated with Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.)

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3

Literatures (Medical) associated with Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.)

01 Nov 2019·Molecular TherapyQ1 · MEDICINE

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

Q1 · MEDICINE

Article

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

02 Mar 2018·Oncotarget

Engineered T lymphocytes eliminate lung metastases in models of pancreatic cancer

Article

Author: Zhao, Yiding ; Yin, Ming ; Wen, Jinhua ; Chen, Jiajia ; Sun, Qiang ; Dong, Jiebin ; Zhao, Jingjing ; Deng, Hongkui ; Teng, Ruidi ; Deng, Changwen ; Bai, Yun ; Zhou, Shixin

Pancreatic cancer is known as one of the most lethal cancers in the world. A majority of advanced stage pancreatic cancer patients are diagnosed with distant metastasis and given poor prognoses, calling for a better therapeutic option. Mesothelin, which is overexpressed in pancreatic cancer and other solid tumors, is a potential target for pancreatic cancer immunotherapy. Adoptive transfer of T cells engineered with chimeric antigen receptors (CART cells) was effective for treating CD19-positive leukemia, but it is more difficult for CART cells to eliminate solid tumors. Because distal metastasis is an important malignant behavior of solid tumors, we investigated whether meso-CART cells exert anti-tumor effects against distant metastases. After expressing meso-CAR in human primary T lymphocytes, the resultant meso-CART cells released cytokines in response to and exhibited cytolytic effects on mesothelin-positive tumor cells in vitro. Injection of meso-CART cells into tumor-bearing mice moderately delayed subcutaneous tumor growth and eliminated lung metastases. This is the first study to show that meso-CART cells are effective against lung metastases induced by intravenous injection of pancreatic tumor cells. Our results suggest that meso-CART cells may be an effective clinical treatment for mesothelin-positive primary and metastatic tumors in pancreatic cancer patients.

01 Apr 2017·Journal of ImmunotherapyQ4 · MEDICINE

Possible Compartmental Cytokine Release Syndrome in a Patient With Recurrent Ovarian Cancer After Treatment With Mesothelin-targeted CAR-T Cells

Q4 · MEDICINE

Article

Author: Maus, Marcela V. ; Plesa, Gabriela ; Porter, David ; Stashwick, Caitlin ; Tanyi, Janos L. ; June, Carl H. ; Morgan, Mark A.

Cytokine release syndrome (CRS) is a potentially severe systemic toxicity seen after adoptive T-cell therapy and caused by T-cell activation and proliferation and is associated with elevated circulating levels of cytokines such as C-reactive protein, interleukin-6 (IL-6), and interferon-γ and has previously been described as a systemic response in hematologic malignancies. A 52-year-old woman with BRCA 1 mutation positive heavily pretreated advanced recurrent serous ovarian cancer was treated under a compassionate use protocol with autologous mesothelin-redirected chimeric antigen receptor T cells (CART-meso). Autologous T cells were transduced to express a receptor composed of an extracellular antimesothelin single-chain variable fragment fused to 4-1BB and TCR-zeta signaling domain. This patient was infused with 3×107 CART-meso T cells/m2 without lymphodepletion and developed compartmental CRS confined to the pleural cavities. The compartmental CRS was evidenced by an increase in IL-6 and accumulation of CART-meso T cells in pleural fluid compared with peripheral blood and was successfully treated the anti-IL6 receptor antagonist tocilizumab on D21 after the T-cell infusion. This is the first description of a compartmental CRS in a patient with solid malignancy. This response could be due to malignant pleural fluid creating an environment where T cells could interact with tumor cells and suggests localized on-target CAR-T-cell activation.

100 Deals associated with Mesothelin CAR-T cell therapy(Shenzhen BinDeBio Ltd.)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Pancreatic Cancer	Phase 3	China	Shenzhen Binde Biotechnology Co., Ltd.	11 Jul 2018
Pancreatic Cancer	Phase 2	China	Jiangsu Provincial People's Hospital	-
Pancreatic Cancer	Phase 2	China	Shenzhen Binde Biotechnology Co., Ltd.	-
Stomach Cancer	Phase 2	China	Jiangsu Provincial People's Hospital	-
Stomach Cancer	Phase 2	China	Shenzhen Binde Biotechnology Co., Ltd.	-