B7-H3-Targeted CAR-T Cells Exhibit Potent Antitumor Effects on Hematologic and Solid Tumors

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• B7-H3 is frequently overexpressed in various cancer types.
• B7-H3 is a promising target for cancer immunotherapy.
• Expression analysis of B7-H3 is crucial for targeted therapies.

Purpose of the Study:

• To analyze B7-H3 mRNA expression across multiple cancer types using TCGA database.
• To generate and evaluate a novel B7-H3-targeted chimeric antigen receptor (CAR) for antitumor activity.
• To assess the potential of B7-H3-targeted CAR-T cell therapy in treating cancers like AML and melanoma.

Main Methods:

• Analysis of B7-H3 mRNA expression in The Cancer Genome Atlas (TCGA) database.
• Generation of a novel B7-H3-targeted CAR.
• In vitro and in vivo testing of CAR-T cell antitumor activity in AML and melanoma models.
• Flow cytometry analysis of B7-H3 expression in AML bone marrow specimens.

Main Results:

• B7-H3 expression was observed to be heterogeneous and variable across cancer types.
• Moderate to high B7-H3 expression was found in some tumor-adjacent tissues, but lower than in tumors.
• B7-H3 expression was absent or very low in normal tissues.
• B7-H3-targeted CAR-T cells demonstrated significant antitumor activity against AML and melanoma in vitro and in vivo.
• Mean B7-H3 expression in AML bone marrow was 57.2%.

Conclusions:

• B7-H3 is a promising pan-cancer target for immunotherapy.
• B7-H3-redirected CAR-T cells effectively control tumor growth.
• Expression heterogeneity and variation of B7-H3 must be carefully considered for clinical translation of CAR-T cell therapy.