The quest for new targets in cancer immunotherapy is driving innovation, and B7-H3 (also known as CD276), a member of the B7 immune checkpoint family, is rapidly emerging as a front-runner. Its high expression across many solid tumors coupled with low expression in normal tissues makes it an attractive target for therapeutic development, with several promising modalities now showing clinical progress.

Key Facts About B7-H3 (CD276)

B7-H3 is a multifaceted protein that influences the tumor microenvironment. Key characteristics include:

• Highly expressed across a wide range of solid tumors (e.g., lung, prostate, breast cancers).

• Low expression in most normal tissues, which helps limit on-target, off-tumor toxicity.

• Associated with poor prognosis in numerous cancer types.

• Expressed as two protein isoforms (2Ig and 4Ig) in humans, which can influence antibody binding and drug design.

The 2025 Clinical Landscape: A Target in Motion

The clinical pipeline for B7-H3-targeted therapies is highly active and diverse.

1. Antibody-Drug Conjugates (ADCs) Take the Lead

ADCs, which deliver potent cytotoxic drugs directly to tumors, are at the forefront. In August 2025, ifinatamab deruxtecan (I-DXd/DS-7300) received FDA Breakthrough Therapy designation for extensive-stage small-cell lung cancer (SCLC). Recent data confirm its strong activity, positioning it as a potential first-in-class B7-H3 ADC.

2. CAR-T Cell Therapies Show Early Promise

Early-phase clinical trials, such as the STRIvE-02 study, have demonstrated that B7-H3-targeting CAR-T cells can be safely administered and show measurable anti-tumor activity in solid tumors. New engineering strategies, including “armored” CARs and dual-antigen targeting, are being explored to enhance their effectiveness.

3. Monoclonal Antibodies and Combinations

Antibodies like enoblituzumab (MGA271) have shown evidence of immune remodeling in cancers like prostate cancer. Research continues into combining these antibodies with other treatments, such as checkpoint inhibitors or radiation therapy.

Beyond Immunity: The Tumor-Intrinsic Roles of B7-H3

Recent research reveals that B7-H3 is more than an immune modulator; it also drives key tumor-intrinsic processes:

• Angiogenesis (formation of new blood vessels to feed the tumor)

• Metabolic reprogramming

• Cancer cell invasion, metastasis, and therapy resistance
  This dual role in both tumor biology and immune evasion makes B7-H3 a compelling target for combination therapies.

Challenges and Future Outlook

Despite the excitement, key challenges remain, including the need to confirm its true receptor(s), develop standardized biomarker assays, and carefully manage potential safety concerns related to low-level expression in some normal tissues.

The outlook is bright. With strong clinical activity and FDA support for leading candidates, B7-H3 is transitioning from a “promising target” to a clinically validated pathway. The coming years will clarify which tumor types and which therapeutic formats—ADCs, CAR-T cells, or bispecific antibodies—will benefit patients most.

How Runtogen Supports B7-H3 Research

At Runtogen, we empower researchers and biotech developers by providing specialized tools to accelerate B7-H3 projects:

• B7-H3 Overexpression Cell Lines for functional assays and drug screening.

• B7-H3 Knockout/Knock-in Models for mechanistic studies.

• Custom Cell Line Engineering tailored to your specific research needs.

👉 Contact us today to discuss how we can support your B7-H3 research and drug development program.