B7-H3/CD276 and small-cell lung cancer: What's new?

• Published in: Translational oncology Vol. 39; p. 101801
• Main Authors: Fabrizio, Federico Pio, Muscarella, Lucia Anna, Rossi, Antonio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2024; Neoplasia Press; Elsevier
• Subjects: ADC; B7-H3; CD276; DS-7300; HS-20093; SCLC; ADC; B7-H3; HS-20093; SCLC; DS-7300; CD276
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2023.101801

•B7-H3, also known as CD276, is a member of the B7 family overexpressed in tumor tissues, including SCLC.•The overexpression of B7-H3 is often correlated with worse survival.•B7-H3 could represent an attractive target for antibody-based immunotherapy.•Combining B7-H3 and other immune checkpoint inhibitors might be a winning strategy.•This review underlines current treatment options and recent clinical trials in pretreated SCLC patients.
Immunotherapy revolutionized the treatment landscape of several cancers, including small-cell lung cancer (SCLC), with a huge number of practice-changing trials, and becoming a new frontier for their management. The addition of an anti-PD-L1, atezolizumab or durvalumab, to platinum/etoposide regimen became the standard of care for first-line therapy of extensive-stage (ES)-SCLC with the 12 months median survival exceeded for the first time.
Nevertheless, most patients show primary or acquired resistance to anti-PD-L1 therefore new promising therapeutic immune-targets are under clinical investigation in several solid tumors. Among these, B7-H3, also known as CD276, is a member of the B7 family overexpressed in tumor tissues, including SCLC, while showing limited expression in normal tissues becoming an attractive and promising target for cancer immunotherapy.
B7-H3 plays a dual role in the immune system during the T-cell activation, acting as a T-cell costimulatory/coinhibitory immunoregulatory protein, and promoting pro-tumorigenic functions such as tumor migration, invasion, metastases, resistance, and metabolism.
Immunohistochemistry, flow cytometry, and immunofluorescence were the most used methods to assess B7-H3 expression levels and validate a possible relationship between B7-H3 staining patterns and clinicopathological features in lung cancer patients.
To date, there are no clinically available therapeutics/drugs targeting B7-H3 in any solid tumors. The most promising preliminary clinical results have been reported by DS7300a and HS-20093, both are antibody-drug conjugates, that are under investigation in ongoing trials for the treatment of pretreated SCLC.
This review will provide an overview of B7-H3 and corresponding inhibitors and the clinical development in the management of SCLC.
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