Source: Sun Yat-sen Memorial Hospital
Edited by: Tan Rongyu, Wang Dongmei

Recently, the research team of Professor Li Jinsong and Associate Professor Fan Song from Sun Yat-sen Memorial Hospital have published their novel findings in Clinical Cancer Research, an internationally renowned oncology journal. The study found that the histone deacetylase inhibitor Vorinostat has a strong synergistic effect on B7-H3.CAR-T cells and significantly enhance the antitumor ability of B7-H3.CAR-T cells on a variety of solid tumors. Professor Li Jinsong, Associate Professor Fan Song, and Professor Soldano Ferrone from the Department of Surgery of Massachusetts General Hospital, Harvard University are the co-corresponding authors; team members Dr. Lei Xinyuan and Dr. Zhanpeng Ou, and Dr. Zhu Yanliang from the School of Life Sciences, Southeast University are the co-first authors of this article.

CAR T cells have produced impressive clinical responses in patients with hematologic malignancies, but the application of CAR T-cell therapy in patients with solid cancers has generated disappointing results to date.

In this research, based on human tissue microarrays, it was found that B7-H3 was broadly expressed across many solid cancer types, but exhibits limited expression in normal tissues. Then the third-generation CAR-T targeting B7-H3 was constructed. At the same time, through the screening of epigenetic regulatory drugs, it displayed that the low-dose histone deacetylase inhibitor Vorinostat (SAHA) and B7-H3.CAR-T cells have a strong synergistic effect. Through high-throughput sequencing and other experiments, it was shown that SAHA can up-regulate the expression of tumor cells B7-H3 and CAR-T cells B7-H3.CAR, and down-regulate the expression of CAR-T cell immunosuppressive molecules CTLA-4 and TET2. Finally, through in vivo and in vitro experiments, it was confirmed that SAHA can significantly enhance the killing ability of B7-H3.CAR-T cells on head and neck squamous cell cancer, triple-negative breast cancer, non-small cell lung cancer, and malignant melanoma. This research provides an important strategy for improving the therapeutic effect of CAR-T cells on solid tumors.

Link to the paper: https://clincancerres.aacrjournals.org/content/27/13/3757