Using AniView100 In Vivo Animal Imaging System to Evaluate the Pancreatic Cancer CAR-T Therapy in Mice

Xudong Zhao's team from the Abdominal Tumor Multimodality Treatment and Laboratory of Animal Tumor Model of West China Hospital of Sichuan University successfully developed and prepared GAS6-CAR-T cells, which proved that the cells can significantly inhibit the growth of pancreatic cancer in vivo and in vitro. This research has been published in the Journal of Hematology & Oncology(IF=28.5, Q1).

Pancreatic cancer is the most lethal malignant tumor. The 5-year survival rate for these patients is less than 10%, 5 years after diagnosis. Chimeric antigen receptor T-cell therapy (CAR-T), as a new cellular immunotherapy, has achieved great success in the treatment of hematological malignancies, and this method has also shown good results in the treatment of solid tumors (including pancreatic cancer). However, CAR-T cells targeting a series of different proteins have not shown significant therapeutic effects on pancreatic cancer in clinical trials, which indicates that it is necessary to explore more effective CAR-T strategies.

Members of the receptor tyrosine kinase TAM (TYRO3, AXL, MERTK) family are overexpressed in a variety of hematologic malignancies, including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoid leukemia, and different types of solid tumors, such as pancreatic cancer, lung cancer, and gastric cancer. The TAM family can promote tumor cell proliferation, invasion, metastasis, drug resistance, and immune escape, and its expression is negatively correlated with the prognosis of cancer patients. Therefore, TAM receptors have become promising therapeutic targets. For example, AXL's small molecule inhibitor BGB324 has entered the phase I/II clinical trial of acute myeloid leukemia and pancreatic cancer. Anti-TYRO3 antibodies can inhibit the carcinogenesis or metastasis of colon cancer and melanoma cells. MERTK monoclonal antibody can promote the apoptosis of triple-negative breast cancer and non-small cell lung cancer.

Xudong Zhao's team generated CAR-T cells based on GAS6 (a natural ligand for all TAM members) and demonstrated that these GAS6-CAR-T cells can effectively kill TAM-positive pancreatic tumor cells and inhibit the growth of xenograft tumors in vivo by eliminating tumor cells and tumor-associated macrophages. The study also demonstrated that GAS6-CAR-T cells can recognize mouse TAM and kill mouse tumor cell lines but have no significant side effects on xenograft mice.

GAS6-CAR-T cells did not produce any significant side effects on non-human primates. This shows that CAR-T cells based on GAS6 are a promising and safe strategy for the treatment of pancreatic cancer.

The effect of GAS6-CAR-T cells on tumor growth in vivo in mice models was observed by using the Biolight Biotechnology AniView series multi-modal in vivo animal imaging system.

▲ A Photographs of NCG mice subcutaneously injected with 5 × 105 PANC1 cells; after receiving CAR-T-cell treatment, tumor volumes were monitored with bioluminescence at the times shown.

Reference:

Fan, J., Yu, Y., Yan, L. et al. GAS6-based CAR-T cells exhibit potent antitumor activity against pancreatic cancer. J Hematol Oncol 16, 77 (2023). https://doi.org/10.1186/s13045-023-01467-9