CAR-T and CAR-NK Immunotherapy for Hepatocellular Carcinoma

Dongfang Liu (Inventor)

Research output: Innovation

Abstract

CAR-NK cells control progression of HCC in PDX model Invention Summary: Chimeric antigen receptor (CAR)-modified T cell therapy has become a promising immune-therapeutic strategy for the treatment of various blood cancers. Hepatocellular carcinoma (HCC) is the most common type of cancer that starts in the liver. HCC is the third most common cause of cancer-related death worldwide. It causes 662,000 deaths worldwide per year. Currently, there is no effective CAR-based immunotherapy to treat HCC. This invention disclosed a new chimeric antigen receptor targeting a surface marker of hepatocellular carcinoma. NK cells transduced with such CAR effectively eliminated malignant hepatocellular carcinoma cells (including SK-Hep1, Huh7, HCO2, Hep3B, and HepG2 cell lines) and primary hepatocellular carcinoma in vitro. Two different xenograft models were used to evaluate whether the CAR-NK can be used to treat HCC in vivo. In the xenograft mouse model, mice receiving the CAR-NK cells were significantly protected from rapid progression of HCC and their median survival was prolonged (P < 0.0001), with comparable body weight among different groups. In the patient derived xenograft (PDX) mouse model of HCC, the median survival of mice treated with the CAR-NK cells was 63 days, which is significantly higher than that of control mice (median survival about 42 days, figure above). These data support the therapeutic potential of RU-CAR-NK or RU-CAR-T cells in patients with HCC. Advantages: - First CAR-based immunotherapy to treat hepatocellular carcinoma. - Strong anti-tumor activities demonstrated both in vitro and in vivo. Market Applications: - CAR-T or CAR-NK therapy for liver cancer. - Can be used to generate "off-the-shelf" CAR-modified cell products Intellectual Property & Development Status: Patent pending. Available for licensing or collaboration
Original languageEnglish (US)
StatePublished - Feb 2020

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