Anti-CD276 Antibody Development

With Ph.D. level scientists and over a decade of experience in recombinant antibody production, antibody engineering, synthetic chemistry, and bio-conjugation, Creative Biolabs is focusing on applying excellent science and technology to discover and develop potential new antibodies with the goal of becoming first-in-class therapeutics, along with providing custom antibody-drug conjugates (ADCs) design and construction services against CD276.

CD276

CD276, also known as B7-H3, is an important immune checkpoint member of the B7 families. Compared with other immune checkpoints, B7-H3 pathway not only regulates innate and adaptive immunity but also promotes cancer cells aggressiveness through various non-immunological functions. CD276 is a 316 amino acid (aa) type I transmembrane glycoprotein belonging to the immunoglobin (Ig) superfamily that contains a putative 28 aa signal peptide, a 217 aa extracellular region with one V-like and one C-like Ig domain, a transmembrane region and a 45 aa cytoplasmic domain. As a result of exon duplication, the extracellular architecture of CD276 is characterized by a single IgV-IgC-like (2IgB7-H3) or IgV-IgC-IgV-IgC-like (4IgB7-H3) domain containing conserved cysteine residues.

Fig.1 Currently known co-stimulatory molecules and their ligands. (Beier, 2007)

CD276 over-expression is associated with most solid tumor types, including many that are in urgent need for better-targeted therapies such as triple-negative breast cancer, pancreatic cancer, and glioblastomas. Over-expressed by tumor cells and vessels but not in the angiogenic vessels of normal tissues makes CD276 an attractive target for the selective destruction of tumor vasculature, providing a dual target for the development of ADCs that can simultaneously destroy both tumor cells and tumor vasculature.

Antibody Therapy against CD276

CD276 was shown to promote invasion and accelerate carcinogenesis in tumor progression according to its non-immunological regulatory roles. Monoclonal antibodies (mAbs) against CD276 could aid in the effective targeting of both angiogenic and non-angiogenic tumor vasculature. Therapeutic approaches in targeting CD276, such as blocking mAbs, bispecific mAbs, chimeric antigen receptor T cells, small molecules inhibitors, and combination therapies have already shown positive results in various cancer settings.

Fig.2 Human cancer immunotherapy strategies targeting CD276. (Picarda, 2016)

As for ADCs, mAbs can be stably conjugated to a biologically active cytotoxic drug or compound that induces cell death. Once the mAb binds the cell surface antigen, the complex is internalized, releasing the cytotoxic substance and killing cancer cells. In an ADC, the antibody acts like a guided missle that directs the drug toward cells that express a specific protein, or signpost. The drug then kills those cells. Pyrrolobenzodiazepine (PBD)-conjugated CD276 ADC killed both cancer cells and tumor vasculature, eradicating large established tumors and metastases, and improving long-term overall survival. CD276-targeted dual-compartment ablation could aid in the development of highly selective broad-acting anti-cancer therapies. Overall, mAbs against CD276 wield its powerful effect on most solid cancer treatment.

Fig.3 PBD dimers are optimal warheads for ADCs targeting CD276. (Seaman, 2017)

With novel technology platform and professional experiment services, Creative Biolabs gets ready to provide you with the best anti-CD276 antibody development services. Please feel free to contact us for more details.

References

1. Beier, K. C.; et al. Master switches of T-cell activation and differentiation. European Respiratory Journal. 2007, 29(4), 804-812.
2. Picarda, E.; et al. Molecular pathways: targeting B7-H3 (CD276) for human cancer immunotherapy. Clinical Cancer Research. 2016, 22(14): 3425-3431.
3. Seaman, S.; et al. Eradication of tumors through simultaneous ablation of CD276/B7-H3-positive tumor cells and tumor vasculature. Cancer cell. 2017, 31(4), 501-515.

For Research Use Only. NOT FOR CLINICAL USE.