Next-IO™ Anti-B7-H3 × CD3 Bispecific Antibody Program

About This Program

This program aims to develop anti-B7-H3 × CD3 therapeutic Bispecific Antibody for immuno-oncology.

Inhibition of the B7-H3 immune checkpoint is reported to limit the growth of B7-H3⁺ tumors. Data have also shown that B7-H3 could serve as a target for T cell-mediated immunotherapy against cancer, making it a promising target for cancer immunotherapy.

B7-H3 × CD3

The CD3 (cluster of differentiation 3) T cell co-receptor is composed of four distinct chains that bind to T cell receptor (TCR) and ζ-chain (ζ-chain) in T lymphocytes to generate an activation signal. In particular, it helps to activate cytotoxic T cells (CD8+ naive T cells) and T helper cells (CD4+ naive T cells).

B7-H3, also known as CD276, is a type I transmembrane glycoprotein that belongs to the B7/CD28 immunoglobulin superfamily. Although receptor interaction with B7-H3 remains unknown, it is supposed to be a coinhibitory receptor in human T cells. Recently scientists have found that:

• B7-H3 protein expression is lower in normal tissues but higher in a wide range of human malignancies.
• By preventing the interaction B7-H3 and its receptor, via direct inhibition or reduced surface expression, immunotherapeutic treatments can decrease tumorigenicity while increasing anti-tumor protein expression.

Fig.1 A graphic presentation of an antigen-presenting cell or tumor cell interacting with a T-cell.

Published Data

Here are some published data about B7-H3 Bispecific Antibody work as a potential target for cancer immunotherapy.

• B7-H3 BiAb-armed activated T cells (ATCs) exhibited increased cytotoxicity against melanoma cells.

(Nature 2019)

• B7-H3 BiAb-armed ATCs secreted more IFN-γ, accompanied by higher levels of activating marker CD69 and CD25 expression.

(Nature 2019)

• Infusion of B7-H3 BiAb-armed ATCs suppressed melanoma growth in a xenograft mouse model.

(Nature 2019)

Indication

B7-H3 has been studied in several solid neoplasms. Its presence has been correlated with worse prognosis and increased the potential to metastasize. Multiple studies have shown that B7-H3 is particularly expressed in non-small-cell lung cancer, breast cancer, prostate cancer, renal cell carcinoma, and brain cancers. Therefore, we intend to develop multiple programs for different indications (not limited to one specific tumor type), in which B7-H3 is highly expressed.

Clinical Trails under Progress

Currently, there are NO clinical studies working on this novel combination therapy. Our program will be the pioneer in the field. While our program focus on CD3 Bispecific Antibody antibodies, future efforts will develop simultaneous multiple interaction T-cell engaging (SMITE) bispecific pairs targeting other co-receptor signaling pathways. In this case, we are incredibly excited about this program and will try our best to make the dual targeting method clinically feasible.

Program Plan

With extensive experience in providing CRO services, we are confident in providing a streamlined end-to-end program. For each program, we are committed to developing a complete program that tailors to the needs of our partners, from antibody discovery, engineering, optimization, to pre-clinical studies. Periodic progress will be delivered to our clients for effective, smooth and timely communications.

Cooperation

Creative Biolabs is looking for potential partners (include but not limited major pharma or biotech firms) to develop anti-B7-H3 × CD3 bispecific antibody program together. Our scientists are dedicated to bringing together years of valuable experience to our partner and achieve a meaningful partnership. By using this strategic collaboration, we hope to help both parties to proceed with IND and many stages of clinical trials beyond.

If you are interested in our program, please feel free to contact us to learn more details about the cooperation. Looking forward to working with you in the near future.

References

• Castellanos J R, et al. B7-H3 role in the immune landscape of cancer.[J]. Am J Clin Exp Immunol, 2017, 6(4): 66-75.
• Ma J., et al. Bispecific anti-CD3 x anti-B7-H3 antibody mediates T cell cytotoxic ability to human melanoma in vitro and in vivo. Invest New Drugs. 2019.