B7-H3 (CD276): Clinical Progress and Emerging Therapeutic Strategies in Solid Tumors

B7-H3 (CD276) Breakthroughs in 2026: From Emerging Target to Clinical Validation

B7-H3 (CD276) is a tumor-associated antigen with high expression in tumor tissues and relatively limited expression in normal tissues, which supports its suitability for targeted therapeutic development.

B7-H3 is highly expressed across a wide spectrum of solid tumors, including lung cancer, prostate cancer, pancreatic cancer, nasopharyngeal carcinoma, osteosarcoma, and pediatric malignancies. Importantly, elevated B7-H3 expression has been associated with tumor progression, metastatic potential, therapeutic resistance, and poor prognosis, while its expression in normal tissues remains relatively restricted. This combination of tumor selectivity and biological relevance has made B7-H3 an attractive candidate for therapeutic intervention.

Over the past several years, this biological rationale has translated into a rapidly expanding pipeline spanning multiple therapeutic modalities, including antibody-drug conjugates (ADCs), bispecific antibodies, radiopharmaceuticals, and cell therapies. Among these, ADCs have progressed most rapidly into clinical-stage development, generating the earliest and most mature efficacy signals in solid tumors.

Clinical Progress Continues to Shape the B7-H3 ADC Landscape

Within the expanding B7-H3 field, several ADC programs have emerged as key clinical references, particularly in lung cancer and prostate cancer, where early efficacy signals are beginning to define the target's therapeutic potential.

HS-20093 Demonstrates Promising Activity in Small Cell Lung Cancer

HS-20093 is a B7-H3-targeted ADC composed of a fully human anti--B7-H3 monoclonal antibody, a tumor microenvironment--responsive linker, and a topoisomerase I inhibitor payload. The design is intended to promote selective intracellular payload release within the tumor while limiting systemic exposure.

Early clinical data in small cell lung cancer (SCLC) have shown encouraging antitumor activity:

- Objective response rate (ORR): 52.3%

- Disease control rate (DCR): 87.7%

- Interstitial lung disease (ILD): 3.4%

- Overall manageable and reversible hematologic toxicity profile

Figure 1. Trial Design, Efficacy, and Safety Profile of HS-20093 in the ARTEMIS-001 Study. (Adapted from Cancer Cell, DOI: 10.1016/j.ccell.2026.02.006)

Taken together, these findings suggest that B7-H3-directed ADCs may represent a promising therapeutic strategy in highly aggressive thoracic malignancies, where treatment options remain limited and response durability is often poor.

DB1311 Expands B7-H3 Validation in mCRPC

Beyond lung cancer, B7-H3-targeted ADCs are also showing activity in genitourinary tumors. DB1311 (BNT324), currently under evaluation in metastatic castration-resistant prostate cancer (mCRPC), has generated early clinical signals of efficacy in heavily pretreated patient populations.

Key findings include:

- Median radiographic progression-free survival (rPFS): 11.3 months

- Objective response rate (ORR): 35.8%

- Disease control rate (DCR): 84.9%

Notably, clinical activity has been observed even in patients previously exposed to radioligand therapies, suggesting a distinct mechanism of action and non-overlapping resistance profile.

With DB1311 advancing into global Phase III evaluation, B7-H3 is increasingly transitioning from an exploratory target to a clinically validated therapeutic axis in prostate cancer.

Figure 2. Phase 1/2 Study Design and Patient Cohorts for DB-1311/BNT324 in mCRPC. (Presented at ASCO GU 2026)

HLX316 Introduces Glyco-Immune Modulation

While cytotoxic drug conjugates dominate the pipeline, innovative non-ADC modalities are exploring distinct biological pathways. One notable example is HLX316, a B7-H3-targeted sialidase fusion protein developed for advanced solid tumors. Rather than relying on cytotoxic payload delivery, HLX316 is designed to enzymatically remove terminal sialic acids from tumor cells.

This strategy aims to reverse glyco-mediated immune suppression within the tumor microenvironment, thereby enhancing endogenous antitumor immune responses. It represents a shift toward glyco-immunology as a complementary therapeutic axis to traditional checkpoint inhibition and ADC-based cytotoxic delivery.

Figure 3. Structural Overview and Glyco-Immune Modulation Mechanism of E-688/HLX316. (Source: Henlius Biotech's presentation at AACR 2025.)

Beyond ADCs: Expanding Therapeutic Strategies Against B7-H3

The accumulation of early clinical efficacy signals across multiple ADC programs has significantly accelerated global investment in B7-H3-directed therapeutics over the past two years.

As of early 2026, more than 60 B7-H3-targeted programs are in development worldwide, including approximately 24 clinical-stage candidates. Among these, ADCs remain the dominant modality, particularly in lung cancer, prostate cancer, nasopharyngeal carcinoma, and osteosarcoma, with several programs already entering late-stage clinical development.

At the same time, the field is clearly expanding beyond ADCs. Radiopharmaceuticals, bispecific antibodies, NK cell engagers, and cell therapies are increasingly being explored.

Cell Therapy Approaches

B7-H3-targeted CAR-T and allogeneic cell therapy programs are currently under investigation. QH104A, an allogeneic CAR-T candidate developed by Qinghui Liannuo Biotechnology Co Ltd., has obtained dual IND approvals in both China and the United States, and is being investigated for the treatment of glioblastoma.

Radiopharmaceutical Development

Given its broad and relatively tumor-selective expression, B7-H3 has also emerged as a promising target for radiopharmaceutical development. Both diagnostic imaging agents and therapeutic radioligands are being explored, supporting applications in precision oncology and patient stratification. RV-01, the first reported B7-H3-targeted radionuclide therapeutic candidate globally, has initiated Phase I/IIa clinical evaluation, with first patient dosing already completed.

Bispecific and Multispecific Antibodies

Bispecific antibodies, including T cell engagers and NK cell engagers targeting B7-H3, are also progressing through early development. These modalities are designed to physically bridge immune effector cells with tumor cells, enabling targeted immune-mediated cytotoxicity.

As engineering platforms evolve, multispecific formats are further expanding the design space of B7-H3-directed immunotherapies.

Future Perspectives: Defining the Role of B7-H3 in Solid Tumors

As clinical data continue to accumulate across ADCs, radiopharmaceuticals, bispecific antibodies, and cell therapies, the clinical characterization of B7-H3 across different therapeutic modalities is becoming more defined, with evidence emerging from multiple tumor types and development stages.

Across these modalities, several key challenges remain active areas of investigation, including the identification of predictive biomarkers for patient stratification, optimization of therapeutic index, and management of on-target toxicities associated with low-level B7-H3 expression in normal tissues.

Research Tools Supporting B7-H3 Drug Development

The rapid expansion of B7-H3-directed therapeutics has also driven strong demand for robust research tools supporting target validation, antibody discovery, and functional characterization across modalities.

Tools provided by ACROBiosystems support end-to-end workflows from early discovery to translational evaluation.

Available solutions include:

- B7-H3 recombinant proteins: Available in 4Ig and 2Ig isoforms, and offered in untagged, biotinylated, and FITC-labeled formats. All proteins are validated by SEC-MALS for purity and confirmed by ELISA/BLI for bioactivity, supporting reliable screening and characterization workflows.

- Biotinylated proteins and pre-coupled magnetic beads：Designed with low nonspecific binding and high capture efficiency, these beads enable efficient antibody enrichment and high-throughput screening applications.

- B7-H3 overexpression cell lines：Validated by FACS for stable and high-level expression, providing robust and reproducible models for cell-based screening, functional validation, and quality control.

B7-H3 Product Portfolio

FAQ

Q: Human B7-H3 naturally exists in both 4Ig and 2Ig isoforms. How does ACROBiosystems ensure structural homogeneity and batch-to-batch consistency for these complex proteins?

A: ACROBiosystems validates all recombinant B7-H3 proteins by SEC-MALS to ensure a highly purified monomeric state with excellent batch-to-batch consistency. Because B7-H3 contains complex multi-domain structures---especially in the 4Ig isoform---recombinant expression can lead to aggregation or conformational heterogeneity that affects antibody screening accuracy. To address this, both 4Ig B7-H3 and 2Ig B7-H3 proteins undergo strict structural verification by SEC-MALS to eliminate multimeric binding artifacts. In addition, every batch is benchmarked by ELISA or BLI for kinetic bioactivity validation, ensuring highly reproducible binding performance for affinity characterization, high-throughput screening (HTS), and therapeutic antibody discovery workflows.

Q: Recombinant B7-H3 is sometimes produced as an Fc-fusion dimer. Does this valency affect the accuracy of true monovalent affinity (KD) measurements during initial clone ranking?

A: Yes. Fc-fusion B7-H3 dimers can introduce avidity effects that artificially enhance apparent binding affinity and mask true KD differences between antibody clones. For accurate SPR or BLI kinetic characterization, ACROBiosystems provides His-tagged and untagged monomeric B7-H3 proteins verified by SEC-MALS. These strictly monomeric formats eliminate avidity-related artifacts and support reliable 1:1 binding analysis. This enables discovery teams to rank antibody candidates based on intrinsic monovalent affinity rather than multivalent binding effects during early-stage clone selection.

Q: For cell-based screening and antibody internalization assays, how do your B7-H3 overexpressing cell lines perform regarding long-term expression stability?

A: ACROBiosystems'B7-H3 overexpressing cell lines are validated for highly stable and uniform target expression across multiple cell passages. Expression drift is a common challenge in cell-based binding and functional assays because inconsistent membrane target density can compromise assay reproducibility. To minimize this risk, ACROBiosystems develops B7-H3 cell lines from single-cell clones and verifies expression stability by FACS across sequential passages. These cell models provide robust and reproducible performance for antibody internalization studies, cytotoxicity assays, functional screening, and routine quality control applications.

Q: Background noise from non-specific binding is a major issue in bead-based antibody enrichment. How do ACRO's pre-coupled B7-H3 magnetic beads address this challenge?

A: ACROBiosystems'pre-coupled B7-H3 magnetic beads are engineered to minimize non-specific binding while maximizing target capture efficiency. The beads utilize site-specific biotinylation and oriented coupling technologies to ensure optimal epitope exposure on the target protein surface. In parallel, the bead matrix undergoes hydrophilic blocking treatment to reduce background adsorption and improve signal-to-noise ratios. This design enables cleaner enrichment results and more reliable recovery of rare or low-affinity therapeutic antibody clones during early-stage screening and panning workflows.