Abstract 5533: YIV-906 could modulate nuclear factor of activated T-cells (NFAT) activity of T cells for immune checkpoint blockade therapy and CAR T-cell therapy

Abstract

Abstract YIV-906 is a standardized botanical drug inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea, and vomiting. Results from seven Phase I/II to II clinical studies suggest that YIV-906 has potential to prolong survival and improve quality of life for patients who have liver, pancreatic, colorectal, and rectal cancer and received chemotherapy and/or radiation therapy. Currently, a phase II international clinical trial for using YIV-906 plus sorafenib to target HBV positive hepatocellular carcinoma as first line therapy (NCT04000737) had been initialized. Recently, we demonstrated that YIV-906 could enhance anti-tumor activity of anti-PD1 against hepatoma in mice by enhancing both adaptive immunity and innate immunity thought promoting T cell activation by modulating IDO activity and potentiating IFNg action to polarize macrophages into M1-like type. Here, by using Jurkat cells-staphylococcal superantigen E (SEE)-Raji cells cell culture model, we demonstrated that YIV-906 could promote T cell activation with up-regulation of CD69 by modulating nuclear factor of activated T-cells (NFAT) activity. This could be due to that YIV-906 could trigger protein phosphorylation of T cell receptor signaling cascades including, Lck, Fyn, Zap70, LAT and Pyk2. Importantly, YIV-906 could enhance Anti-PD1 action to recuse the depressed NFAT activity of Jurkat cells-PD1 cells when incubated with Raji-PD-L1 cells. In addition, YIV-906 could also enhance NFAT activity triggered by the interaction of chimeric antigen receptor (CAR-CD19-CD3z) on Jurkat cells and CD19 on Raji cells. Component S (Scutellaria baicalensis Georgi) of YIV-906 was found to play key roles of the above activities. Flavonoids of S, such as baicalein, chrysin and oroxylin A, were identified to have modulation effect on NFAT activity. In conclusion, YIV-906 could modulate both adaptive immunity and innate immunity to facilitate immune checkpoint blockade therapy or CAR T-cell therapy for treatment of cancer in patients. This is worthy of further investigation. (Supported by research fund from Yiviva, inc) Citation Format: Wing Lam, Shwu-Huey Liu, Peikwen Cheng, Yung-Chi Cheng. YIV-906 could modulate nuclear factor of activated T-cells (NFAT) activity of T cells for immune checkpoint blockade therapy and CAR T-cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5533.