Next-IO™ Anti-PD-L1 × CD28 Bispecific Antibody Program

About This Program

This program aims to develop anti-PD-L1 × CD28 therapeutic Bispecific Antibody for immuno-oncology.

T cell-based cancer immunotherapy has succeeded clinically on certain patients. In particular, Bispecific Antibody recognize both T cells and cancer cells with a broad range of applications. Bispecific Antibody has attracted increasing attention as novel cancer immunotherapy.

PD-L1 × CD28

CD28 is a differentiation antigen expressed on thymocytes and most mature T cells, including all CD4 T cells and CD8 T cells with cytolytic activity. As is known, CD28 is now at the forefront of the field which has been called “T cell co-stimulation”. In addition to its costimulatory role, studies have demonstrated that CD28 ligation can enhance the production of various cytokines, such as IL-2, IL-4, and IL-10.

PD-L1 acts as an inhibitory ligand expressed at the surface of the cancer cells. Binding of the T cell to PD-L1 blocks T cell activation.

Recently scientists have found that:

• PD-L1 inhibition could be overturned by designing a CD28/PD-L1 Bispecific Antibody to trigger the CD28 costimulatory signaling instead of the inhibitory signaling pathway.

Fig.1 Model of T cell engagement by CD3 Bispecific Antibody and CD28 BiTE. (Correnti, 2018)

Published Data

To the best of our knowledge, there are few studies on anti-PD-L1 × CD28 BITE. Further studies are required to dissect the efficacy, safety, and combination strategies. Here we show the published data about anti-PD-L1 × CD28 Bispecific Antibody as a potential target for cancer immunotherapy.

• PD-L1/CD28 Bispecific Antibody can reverse checkpoint inhibition into T-cell activation to overcome Bispecific Antibody resistance.



• T-cell co-activation with the PD-L1/CD28 Bispecific Antibody was strictly dependent on the engagement of CD3 with CD19/CD3.

Clinical Trials under Progress

Currently, there are NO clinical studies on the novel PD-L1 × CD28 BITE. While our program focuses on CD28 Bispecific Antibody antibodies, we also aim to 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 do our best to make the dual targeting method clinically feasible.

Program Plan

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

Collaboration

Creative Biolabs is looking for potential partners (including pharma or biotech firms) to co-develop anti-PD-L1 × CD28 Bispecific Antibody program. Our scientists are dedicated to bringing together years of valuable creation experience and research to explore strategic collaborations with our partner. This business strategy will enable both of us to proceed through IND and go beyond all stages of clinical trials.

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

Reference

• Correnti C E., et al. Simultaneous multiple interaction T-cell engaging (SMITE) bispecific antibodies overcome bispecific T-cell engager (BiTE) resistance via CD28 co-stimulation [J]. Leukemia, 2018, 32(5): 1239.