B7-H3 in Cancer Immunotherapy—Prospects and Challenges: A Review of the Literature

• Published in: Cells (Basel, Switzerland) Vol. 14; no. 15; p. 1209
• Main Authors: Mielcarska, Sylwia, Kot, Anna, Dawidowicz, Miriam, Kula, Agnieszka, Sobków, Piotr, Kłaczka, Daria, Waniczek, Dariusz, Świętochowska, Elżbieta
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.08.2025; MDPI
• Subjects: Animals; B7 Antigens - immunology; B7 Antigens - metabolism; B7-H3 (CD276); B7-H3 clinical trials; Biological products; Brain cancer; Brain tumors; Cancer; Cancer immunotherapy; Cancer therapies; Care and treatment; Cell growth; Clinical trials; Colorectal cancer; Cytokines; Cytotoxicity; Dendritic cells; Development and progression; Glioblastoma; Gliomas; Humans; immune checkpoint; Immune checkpoint inhibitors; Immune response; Immunology; Immunotherapy; Immunotherapy - methods; Literature reviews; Lung cancer; Lymphocytes; Lymphocytes T; Malignancy; Melanoma; Molecular modelling; Monoclonal antibodies; Neoplasia; Neoplasms - immunology; Neoplasms - therapy; Neuroblastoma; Neuroblasts; Patients; Pituitary; Prognosis; Prostate cancer; Review; solid tumors; Squamous cell carcinoma; T cells; Transcription factors; Tumor necrosis factor-TNF; Tumorigenesis; Tumors; New Brunswick; B7-H3 (CD276); solid tumors; immune checkpoint; B7-H3 clinical trials
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells14151209

In today’s oncology, immunotherapy arises as a potent complement for conventional cancer treatment, allowing for obtaining better patient outcomes. B7-H3 (CD276) is a member of the B7 protein family, which emerged as an attractive target for the treatment of various tumors. The molecule modulates anti-cancer immune responses, acting through diverse signaling pathways and cell populations. It has been implicated in the pathogenesis of numerous malignancies, including melanoma, gliomas, lung cancer, gynecological cancers, renal cancer, gastrointestinal tumors, and others, fostering the immunosuppressive environment and marking worse prognosis for the patients. B7-H3 targeting therapies, such as monoclonal antibodies, antibody–drug conjugates, and CAR T-cells, present promising results in preclinical studies and are the subject of ongoing clinical trials. CAR-T therapies against B7-H3 have demonstrated utility in malignancies such as melanoma, glioblastoma, prostate cancer, and RCC. Moreover, ADCs targeting B7-H3 exerted cytotoxic effects on glioblastoma, neuroblastoma cells, prostate cancer, and craniopharyngioma models. B7-H3-targeting also delivers promising results in combined therapies, enhancing the response to other immune checkpoint inhibitors and giving hope for the development of approaches with minimized adverse effects. However, the strategies of B7-H3 blocking deliver substantial challenges, such as poorly understood molecular mechanisms behind B7-H3 protumor properties or therapy toxicity. In this review, we discuss B7-H3’s role in modulating immune responses, its significance for various malignancies, and clinical trials evaluating anti-B7-H3 immunotherapeutic strategies, focusing on the clinical potential of the molecule.