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Clinical Pipelines › GPC1 CAR-T therapy

Cellular immunotherapy for solid tumors such as esophageal cancer

Glypican 1-Specific CAR-T Therapy

in anti-Glypican 1 chimeric antigen receptor T-cell therapy (GPC1 CAR-T therapy), T cells are extracted from the patient’s blood, modified with the GPC1 CAR-T gene to target solid tumors, and then reinfused into the patient. The GPC1 CAR-T cells recognize and attack the solid tumors.

Treatment Concept

Clinical pipeline - GPC1 CAR-T - treatment concept

 

Mechanism of Action

T cells extracted from the patient’s blood are engineered to create GPC1 CAR-T cells by incorporating a monoclonal antibody that recognizes GPC1. These modified GPC1 CAR-T cells are then expanded in large quantities and administered to the patient. After administration, the GPC1 CAR-T cells specifically recognize GPC1, which is specifically expressed on solid tumors such as esophageal cancer, and powerfully attack and destroy the cancer cells expressing GPC1.

Clinical pipeline - GPC1 CAR-T - mechanism of action

 

Therapeutic Indications

Squamous Cell Carcinomas, Including Esophageal Cancer

Conventional CAR-T therapy has demonstrated high therapeutic efficacy in hematologic malignancies such as leukemia and malignant lymphoma, and some have already been approved. On the other hand, in solid tumors, no suitable CAR-T targets had been clearly identified, and therapeutic efficacy had not been demonstrated.

To address this challenge, GPC1 was newly identified as a target for CAR-T therapy in solid tumors.GPC1 is expressed specifically in solid tumors such as squamous cell carcinoma and pancreatic cancer, while it is not expressed in normal adult tissues.

This therapy is expected to be effective against solid tumors in which GPC1 is expressed on the cancer cell membrane.

Cases in which GPC1 expression on the cancer cell surface was confirmed and their proportion[1 – 5]

Esophageal cancer 98.8%
173/175 cases
Clinical pipeline - GPC1 CAR-T - pie chart 98.8%

 

Cervical cancer 91.2%
62/68 cases
Clinical pipeline - GPC1 CAR-T - pie chart 91.2%

 

Head and neck cancer 72.4%
118/163 cases
Clinical pipeline - GPC1 CAR-T - pie chart 72.4%

 

Lung squamous cell carcinoma 100%
63/63 cases
Clinical pipeline - GPC1 CAR-T - pie chart 100%

 

Pancreatic cancer 59.7%
111/186 cases
Clinical pipeline - GPC1 CAR-T - pie chart 59.7%

 

[1] Hara H, et al. Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma. Br J Cancer. 2016 Jun 28;115(1):66-75PMID: 27310703.

[2] Matsuzaki S, et al. Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer. Int J Cancer. 2018 Mar 1;142(5):1056-1066. PMID: 29055044.

[3] Farnedi A, et al. Proteoglycan-based diversification of disease outcome in head and neck cancer patients identifies NG2/CSPG4 and syndecan-2 as unique relapse and overall survival predicting factors. BMC Cancer. 2015 May 3;15:352. PMID: 25935541.

[4] Kai Y, et al. Glypican-1 is a novel immunohistochemical marker to differentiate poorly differentiated squamous cell carcinoma from solid predominant adenocarcinoma of the lung. Transl Lung Cancer Res. 2021 Feb;10(2):766-775. PMID: 33718020.

[5] Lu H, et al. Elevated glypican-1 expression is associated with an unfavorable prognosis in pancreatic ductal adenocarcinoma. Cancer Med. 2017 Jun;6(6):1181-1191. PMID: 28440066.

Status of Development Progress

In Japan, in December 2024, REPROCELL was were selected for the AMED public solicitation project 'Development of foundational technologies for the industrialization of regenerative medicine and gene therapy.

GPC1 CAR-T
R&D
Pre-clinical
Clinical Trial
Approval
GPT1 CAR-T
 

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