Almost every pharmaceutical practitioner knows about the famous CAR-T, the emergence of which represented major progress in personalized cancer treatment and has especially brought the hope of rebirth to patients with hematological malignant tumors. 2017 was called the first year of the era of CAR-T cell therapy because the FDA successively approved the first two commercial CAR-T cell therapy products in 2017, which are also the only two at present: Novartis' Kymriah (lymphoma) and Gilead's Yescarta (leukemia), opening a new era of cancer immunotherapy.
Like all other forms of cancer immunotherapy, CAR-T cell therapy is expected to strengthen the internal anti-cancer ability of the immune system. It is essentially introducing the chimeric antigen receptor (CAR) into the T cell to produce a T cell that specifically identifies the tumor. Once the receptor is expressed by a T cell, a single fusion molecule can be used to specifically bind to the antigen and activate the T cell. What is most important about this technique is that it can produce a large number of T cells that kill tumors within a relatively short time, which has enabled this technique to be used clinically.
However, currently, CAR-T cell therapy mainly has significant effects against blood tumors because there is a traditional target in the tumor cells of blood tumors-CD19 (only existing in tumor cells, not existing in normal cells). CAR-T cells can be easily led to cancer cells by relying on this target, to wipe out cancer. However, there is no such apparent target that only exists in tumor cells instead of normal cells in solid tumors.
The medical community has been expecting CAR-T cells to have new specific targets in more solid tumors.
Here it is: the brand-new solid tumor target of CAR T cells-claudin18.2
Claudin18.2 (CLDN18.2), a gastric-specific membrane protein, has been regarded as a potential therapeutic target for gastric cancer and other cancer types. Based on this, Chinese researchers have developed the world's first CAR-T cell that targets claudin18.2.
According to the official website of the National Medical Products Administration of China (NMPA) on May 27, the clinical trial application for the anti-claudin18.2 (CLDN18.2) autologous CAR-T cell therapy (CT041) independently developed by CARsgen Therapeutics has been accepted by the NMPA. Claudin18.2 (CLDN18.2) is highly expressed in gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, and pancreatic cancer, etc. and is considered as a therapeutic target of those malignant tumors.
The Investigational New Drug (IND) application of this CAR-T cell therapy has also been approved by the U.S. FDA to treat advanced gastric and pancreatic cancers. It is understood that this is the first CLDN18.2-targeted CAR-T cell therapy IND cleared for clinical trials in the world and is of great significance to patients with advanced gastric and pancreatic cancers.
At the CAR-TCR Summit held in Boston, the U.S. in Sep. 2018, the Chinese enterprise committed to developing CAR-T cell immunotherapy published the clinical data of its CAR-Claudin18.2 T-cell clinical trial in pancreatic/gastric cancer patients.
Among 12 patients enrolled, 8 were observed with tumor regression of different degrees. In an improved sub-cohort of 6 subjects, 5 patients (including 1 to be confirmed the objective response) showed objective response including 1 patient of complete response per RECIST 1.1 criteria.
The study was updated its data at the 2019 ASCO Annual Meeting: 12 subjects with metastatic adenocarcinoma (7 gastric and 5 pancreatic) were treated with claudin18.2-specific CAR-T cell therapy, and there were no serious adverse events, treatment-related death or severe neurotoxicity occurred in the study.
Among the 11 evaluable subjects, 1 achieved a complete response (gastric adenocarcinoma), 3 had partial responses (2 gastric adenocarcinomas and 1 pancreatic ad...
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