B7-H3-targeted CAR-T cell therapy for solid tumors

Abstract

Since B7-H3 is overexpressed or amplified in many types of solid tumors with a restricted expression in the normal tissues, it has been an emerging immunotherapeutic target for solid tumors. This review will focus on the structural designs of developing chimeric antigen receptors (CARs) targeting B7-H3. The expression, receptor, and function of the B7-H3, as well as a short overview of B7-H3-targeted monoclonal antibody therapy, are discussed. Finally, a detailed summary of B7-H3 redirected CAR-T and CAR-NK cell approaches utilized in preclinical models and currently ongoing or completed clinical trials are presented. It has been demonstrated that B7-H3-targeted CAR-based cell therapies were safe in initial trials, but their efficacy was limited. Employing the local delivery routes, the introduction of novel modifications promoting CAR-T persistence, and combined treatment with other standard therapies could improve the efficacy of B7-H3-targeted CAR-T cell therapy against solid tumors.

Graphical Abstract

Cancers develop by avoiding being discovered and destructed by the immune system. Cancer immunotherapy is characterized as an approach to assist the immune system to recognize and fight cancer by using uses some substances. Chimeric antigen receptor (CAR) is a protein designed to recognize a target of interest on tumor cells, immune cells armed with which are able to treat human cancers. B7-H3 is a type I transmembrane protein overexpressed in various solid tumors but scarcely detected in normal tissues. Moreover, it is associated with a poor prognosis for many cancer patients. Therefore, we discussed the role of B7-H3 in solid tumors, and concluded it as a promising therapeutic target for CAR-based immunotherapy. A number of B7-H3 CARs have been developed and tested in recent years, but which CAR construct targeting B7-H3 works best remains uncertain. Up till now, the design of B7-H3 CARs is still controversial and challenging. Hence, we summarized and compared the designs and efficacies of B7-H3 CARs utilized in preclinical models and currently ongoing or completed clinical trials in this review, and aimed to provide a better reference for future B7-H3 CAR design.

Keywords:

• B7-H3
• CAR-T
• solid tumors

Acknowledgement

This review benefited from the open data from the the Human Protein Atlas, Cancer Genome Atlas, Cancer Cell Line Encyclopedia database, and the ClinicalTrials database. Figure 1 and Figure 4 were created with BioRender.com.

Compliance with ethics guidelines

Guangfei Li, Haopeng Wang, Haitao Wu and Jian Chen declare that no competing interest exists. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

Disclosure statement

The authors report no declaration of interests.

Data availability statement

All data generated or analyzed during this study are included in this published article.

Table 1. A summary of recent reports based on chimeric antigen receptor (CAR) T and chimeric antigen receptor (CAR) NK cell therapies to target B7-H3 positive tumor cells.

Additional information

Funding

This research received grant from Youth Foundation of National Natural Science Foundation of China (82102863), Original Exploration Project of Shanghai Natural Science Foundation (21ZR1480200), Shanghai Technology Innovation Project (21Y11912000), and individualized support project for original scientific research of Fudan University (IDF158017/015).