CARsgen develops CAR-T cell immunotherapy for liver cancer

CARsgen completed a Series A funding of an undisclosed amount led by BVCF (百奥财富). The company plans to initiate clinical studies for its lead candidate KJgpc3-001, an genetically modified T cell which expresses a third-generation GPC3-targeted chimeric antigen receptor (CAR). KJgpc3-001 was designed by scientists from Shanghai Jiaotong University.

GPC3 (glypican-3) is highly expressed in hepatocellular carcinoma (HCC) but limited expressed in normal tissues (63.6% vs. 9.2%)[1]. Unfortunately, no partial or complete response was observed in the phase I study of anti-GPC3 monoclonal antibody GC33[2]. However, a GPC3-derived vaccine seemed effective in patients with HCC. In the 33 patients phase I study[3], the disease control rate was 60.6% and the median overall survival was 9.0 months.

KJgpc3-001 comprises anti-GPC3 scFv derived from GC33 and intracellular signaling domain derived from CD28/4-1BB/CD3ζ[4]. KJgpc3-001 could be transduced into patient’s T cells with the lentiviral vector to attack the liver cancer. In preclinical studies, all mice treated with KJgpc3-001 survived for longer than 60 days, while the median survival of the saline-treated mice was 33 days.

A major concern about KJgpc3-001 is the expression of GPC3 in normal tissues such as gastric glands, kidney tubules, and germ cells[1]. Previously, one patient with breast cancer died after the treatment with HER2-targeted CAR due to the expression of HER2 in lung tissues[5]. The patient experienced respiratory distress within 15 minutes after cell infusion and died 5 days after treatment.

[1] Am J Clin Pathol. 2008, 129(6), 899-906.

[2] Clin Cancer Res. 2013, 19(4), 920-928.

[3] Clin Cancer Res. 2012, 18(13), 3686-3696.

[4] Clin Cancer Res. 2014, doi: 10.1158/1078-0432.CCR-14-1170.

[5] Mol Ther. 2010, 18(4), 843-851.

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