B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer

Shibao Li; Miaomiao Zhang; Meng Wang; Haiting Wang; Han Wu; Lijun Mao; Meng Zhang; Huizhong Li; Junnian Zheng; Ping Ma; Gang Wang

doi:10.1038/s41420-023-01453-7

B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer

Cell Death Discov. 2023 May 6;9(1):147. doi: 10.1038/s41420-023-01453-7.

Authors

Shibao Li^#^{1

2}, Miaomiao Zhang^#¹, Meng Wang^{3

4

5}, Haiting Wang², Han Wu², Lijun Mao⁶, Meng Zhang⁶, Huizhong Li^{3

4

5}, Junnian Zheng^{7

8}, Ping Ma⁹, Gang Wang^{10

11

12}

Affiliations

¹ Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
² Department of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
³ Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
⁴ Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
⁵ Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
⁶ Department of Urology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
⁷ Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. jnzheng@xzhmu.edu.cn.
⁸ Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. jnzheng@xzhmu.edu.cn.
⁹ Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. pingm62@aliyun.com.
¹⁰ Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. wangg@xzhmu.edu.cn.
¹¹ Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. wangg@xzhmu.edu.cn.
¹² Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. wangg@xzhmu.edu.cn.

^# Contributed equally.

Abstract

B7-H3 is an attractive target for immunotherapy because of its high expression across multiple solid tumors, including prostate cancer, and restricted expression in normal tissues. Among various types of tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematological tumors. However, the potency of CAR-T cell therapy in solid tumors is still limited. Here, we examined the expression of B7-H3 in prostate cancer tissues and cells and developed a second-generation CAR that specifically targets B7-H3 and CD28 as costimulatory receptor to explore its tumoricidal potential against prostate cancer in vitro and in vivo. The high expression of B7-H3 was detected on both the surface of PC3, DU145 and LNCaP cells and prostate cancer tissues. B7-H3 CAR-T cells efficiently controlled the growth of prostate cancer in an antigen-dependent manner in vitro and in vivo. Moreover, tumor cells could induce the proliferation of CAR-T cells and the release of high levels of cytokines of IFN-γ and TNF-α in vitro. Results demonstrated that B7-H3 is a potential target for prostate cancer therapy that supports the clinical development of B7-H3 specific CAR-T cells for prostate cancer.