As a thriving CRO, Creative Biolabs focuses on developing novel therapeutic antibody programs with the goal to treat cancer. We have proposed a variety of Next-IO™ programs with different promising targets or combined targets before. The programs include a full spectrum of targets, such as T cell, B cell, NK cell, dendritic cell, and macrophage, etc. This anti-2B4 monoclonal antibody program aims to develop therapeutic mAb that could activate NK cell immune responses to attack cancer cells.

2B4

2B4, also known as CD244, is an immunoglobulin Signalling Lymphocytic Activation Molecule, also known as CD150 (SLAM) family receptors. It’s structurally related to CD2. Originally, 2B4 was identified as a membrane molecule involved in non-MHC restricted cytotoxicity mediation by NK and CD8+ T cells. It is expressed on all NK cells, and some subsets of other populations including γδ T cells, memory αβ T cells, granulocytes, monocytes, and mast cells. Now, it’s further characterized (see Fig. 1). CD48, a glycosylphosphatidyl-inositol-linked member of the CD2 family, is the ligand for 2B4. Studies have indicated 2B4 deficient mice exhibit greater anti-tumor efficacy than wild-type NK cells. These studies suggest 2B4 plays an inhibitory receptor in the pathway. Therefore, we propose a program to utilize the anti-tumor function by blocking 2B4.

Our Anti-2B4 Antibody Program

When crosslinking to CD48 or other antibodies, 2B4 will increase the level of cytotoxicity and cytokine production. 2B4 is highly expressed on virus-specific CD8+ T cells, and blocking 2B4 with anti-2B4 antibodies can restore T cell immune function. All these findings support 2B4 to be a potential immuno-therapeutic target. This inspires us to develop therapeutic antibodies that work in higher titer, safer and efficient when targeting 2B4. Except for the program on monoclonal antibody, we are also open to developing combination strategies, and other antibody modalities, such as a bispecific antibody, etc.

Published Data

• Ligation of 2B4 by CD48 expressed on tumor cells inhibits NK cytotoxicity.

Fig.1 Ligation of 2B4 by CD48 expressed on tumor cells inhibits NK cytotoxicity.¹

• Engagement of 2B4 inhibits NK rejection of tumor cells in vivo.

Fig.2 Engagement of 2B4 inhibits NK rejection of tumor cells in vivo.¹

• B16 melanoma cell growth is suppressed in 2B4^-/- mice.

From the data, we learn that the 2B4 is identified as an inhibitory receptor expressed on NK cells. For any additional assistance, please feel free to reach out to our scientists.

Program Planning and Management

We have extensive experience in performing comprehensive program developments and effective problem-solving. For our Next-IO™ programs, we are committed to promoting the program to the pre-IND stage within about 1.5 years. The accurate timeline will be determined on a case-by-case basis. Here is a draft timeline for your glance.

Fig.3 The timeline of Next-IOᵀᴹ programs.

Collaboration

Creative Biolabs is looking for potential partners and collaboration opportunities to co-develop the anti-CD48 antibody program. We offer trusted partnerships to partners all over the world. We are committed to forward the project as soon as possible to ensure timely delivery. We will acknowledge and share the potential risks with our clients together. We firmly believe the powerful collaboration will unleash the creative spirit and help both parties reach new horizons in the field of immuno-oncology.

If you are interested in the collaborations, please don’t hesitate to contact us to learn more.

Reference

• Lee, Kyung-Mi et al. "2B4 acts as a non-major histocompatibility complex binding inhibitory receptor on mouse natural killer cells." The Journal of experimental medicine. 199,9 (2004): 1245-54.

For Research Use Only | Not For Clinical Use