B7-H3: Broad Prospects of Emerging Tumor Immunotherapy Targets

Recently, in the renowned academic journal Nature Medicine, the Kimmel Cancer Center at Johns Hopkins University published Phase 2 clinical results regarding enoblituzumab, a monoclonal antibody targeting B7-H3, for the treatment of prostate cancer. The results demonstrate that enoblituzumab can successfully induce the body's anti-cancer activity, showing favorable therapeutic efficacy and safety for patients with high-risk or very high-risk prostate cancer. B7-H3 is expressed in limited amounts in normal tissues but is highly expressed in various cancers, including prostate cancer cells. It is involved in the formation and development of the tumor microenvironment (TME) and plays an important role in regulating immune responses. Researchers state that enoblituzumab, as a new treatment approach, primarily works by relieving the inhibition of the immune system's recognition and elimination of cancer cells by B7-H3. It triggers the physiological process of antibody-dependent cell cytotoxicity (ADCC), activating cytotoxic immune cells such as macrophages and natural killer cells to eliminate tumor cells. Through 30 months of follow-up monitoring, none of the 32 enrolled patients showed detectable prostate-specific antigen (PSA) levels 12 months after prostatectomy. The drug has been proven to be well-tolerated, with no reports of surgical delays or medical complications during or after surgery. Dr. Eugene Shenderov, the lead author of the study, stated that the use of B7-H3-targeted immunotherapy in prostate cancer is feasible and safe, with preliminary data showing potential clinical activity. The anti-cancer efficacy of enoblituzumab will be further evaluated in larger-scale clinical trials. Enoblituzumab may become the first antibody-based immunotherapy for the treatment of prostate cancer. [1]

Introduction: B7-H3
B7-H3 belongs to the B7 family, which includes 10 known members: B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1), B7-DC (PD-L2), B7-H2 (CD275), B7-H3 (CD276), B7-H4 (VTCN1), B7-H5 (VISTA), B7-H6 (NCR3LG1), and B7-H7 (HHLA2). Cancer immunotherapy based on immune evasion mechanisms, represented by B7-H1 (PD-L1) targeting (anti-PD therapy), has achieved higher objective response rates in patients and significantly reduced immune-related adverse events. This indicates that immunomodulatory therapy for tumors has matured, and with further research, clinical efficacy has been confirmed.

The B7-H3 gene is located on mouse chromosome 9 and human chromosome 15q24. The human B7-H3 gene consists of 9 exons, and due to exon duplication, it exists in two isoforms: 2IgB7-H3 and 4IgB7-H3. B7-H3 exists in soluble and membrane-bound forms, and soluble B7-H3 (sB7-H3) is released from the cell surface through the action of matrix metalloproteinases (MMPs). B7-H3 is expressed in non-immune cells such as synovial cells, osteoblasts, endothelial cells, and can also be induced on the surface of immune cells, including dendritic cells, monocytes, and B cells. Initially considered a co-stimulatory molecule, human B7-H3 protein enhances the proliferation of CD4+ and CD8+ T cells and enhances cytotoxic T cell activity in the presence of anti-CD3 antibodies. In addition to its co-stimulatory function, B7-H3 also has a co-inhibitory role in anti-tumor immunity. Studies have shown that B7-H3 may inhibit the proliferation of CD4+ and CD8+ T cells by suppressing the nuclear factor NF-κB and signal transducer and activator of transcription 1 (STAT1) pathways activated in activated T cells, leading to a decrease in the production of IL-2 and IFN-γ. During T cell activation, B7-H3 effectively and continuously suppresses T cell proliferation and the production of IFN-γ, IL-13, IL-10, and IL-2. In addition to its inhibitory effect on T cells, B7-H3 also suppresses NK cell activity. The immunosuppressive microenvironment shaped by B7-H3 helps cancer cells avoid immune destruction. [2]

Strategies for Targeting B7-H3 in Immunotherapy
The advantages of developing targeted drugs against B7-H3 in immunotherapy are as follows: (1) B7-H3 is expressed in most tumors, and inhibiting this target can significantly impact tumor growth by suppressing tumor anti-apoptosis, proliferation, metabolism, and promoting angiogenesis; (2) The discovery of this target is relatively recent, offering promising prospects for development; (3) There are multiple proteins within the same family as this target, and most of them are highly expressed in tumors, facilitating the design of combination therapies.

Currently, there are several tumor immunotherapy strategies based on B7-H3: (A) Targeting B7-H3 with blocking monoclonal antibodies; (B) Targeting B7-H3 through ADCC (antibody-dependent cell-mediated cytotoxicity); (C) Targeting B7-H3 through ADC (antibody-drug conjugate) therapy; (D) Targeting B7-H3 with CD3-engaging bispecific antibodies (BsAbs); (E) BiKEs (bispecific killer cell engagers) and TriKEs (trispecific killer cell engagers); (F) Targeting B7-H3 with small molecule inhibitors; (G) Targeting B7-H3 with CAR-T cells and CAR-NK cells; (H) Synergistic therapies with anti-B7-H3 therapy. [2]

Beta Lifescience provides a series of B7-H3 target proteins that are suitable for various applications, including animal immunology, screening of B7-H3 targeted drugs, functional evaluation, and quality control, among other different stages.

Recommended B7-H3 Products

Recombinant Human B7-H3 (C-6His)

Recombinant Mouse B7-H3 (C-6His)

Recombinant Cynomolgus B7-H3 (C-6His)

Recombinant Cynomolgus B7-H3 (C-Fc)

Other Related Products

Recombinant Human B7-1 (C-6His)

Recombinant Human B7-1 (C-mFc)

Recombinant Rat B7-1 (C-6His)

Recombinant Mouse B7-1 (C-6His)

Recombinant Mouse B7-1 (C-Fc)

Recombinant Cynomolgus B7-1 (C-6His)

Recombinant Cynomolgus B7-1 (C-Fc)

Recombinant Rabbit B7-1 (C-6His)

Recombinant Human B7-2 (C-6His)

Biotinylated Human B7-2 (C-Avi-6His)

Recombinant Mouse B7-2 (C-6His)

Recombinant Mouse B7-2 (C-Fc)

Recombinant Rhesus Macaque B7-2 (C-6His)

Recombinant Cynomolgus B7-2 (C-Fc)

Recombinant Rabbit B7-2 (C-6His)

Recombinant Mouse B7-H2 (C-6His)

Recombinant Human B7-H4 (C-Fc)

Recombinant Human B7-H4 (C-mFc)

Biotinylated Human B7-H4 (C-Fc-Avi)

Recombinant Mouse B7-H4 (C-Fc)

Recombinant Human B7-H6 (C-6His)

Reference
[1] Shenderov, Eugene et al. “Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial.” Nature medicine vol. 29,4 (2023): 888-897. doi:10.1038/s41591-023-02284-w

[2] Zhou WT, Jin WL. B7-H3/CD276: An Emerging Cancer Immunotherapy. Front Immunol. 2021 Jul 19;12:701006. doi: 10.3389/fimmu.2021.701006. PMID: 34349762; PMCID: PMC8326801.