Compared with traditional therapies, monoclonal antibody-based immunotherapy is thought to be more advantageous. In recent years, impressive therapeutic mAbs are approved to treat cancer, such as anti-PD1 mAb, anti-CTLA4 mAb, etc. As a thriving CRO, Creative Biolabs Next-IO™ team is dedicated to developing novel therapeutic mAb programs with the help of our partners across all targets. This anti-HLA-G mAb program aims to develop therapeutic mAb against HLA-G that could potentially restore the cytotoxicity activity of NK cells.

HLA-G

Human leukocyte antigen-G (HLA-G), a non-classical HLA molecule and a major histocompatibility complex class I (MHC-I) antigen, is one of the most characterized molecules so fat. In the norm, HLA-G is expressed in fetal tissues, cells of hematopoietic lineage, and adult immune-privileged organs under physiological conditions. However, it is highly expressed in cancer cells under pathological conditions. As a ligand for the inhibitory NK receptors, KIR2DL4, HLA-G can upregulate tumor-promoting agents and their ligation can interfere with NK cell-mediated cytotoxicity. Furthermore, the expression of HLA-G has been found to associate with poor prognosis in patients with cancer. All the above data imply HLA-G may play a role in tumor evasion. From this, we propose this mAb program against HLA-G to suppress the tumor immune evasion and hopefully, restore the NK cell-mediated cytotoxicity.

Here are the key features of HLA-G:

• Expression of HLA-G and plasma sHLA-G levels in cancer are associated with clinical parameters;
• HLA-G polymorphisms is a condition that could further cancer progression;
• HLA-G is proved to be involved in cancer development.

Our Anti-HLA-G Antibody Program

All these findings of HLA-G inspire us to develop the therapeutic antibodies that work in higher titer, safer and efficient when targeting. We are dedicated to promoting anti-HLA-G immunotherapy into the pre-IND stage. Except for the program on monoclonal antibody, we are also open to developing combination strategies, and other antibody modalities, such as a bispecific antibody, HLA-G peptide, etc.

Published Data

• HLA-G expression level is high in a gastric cancer model.
• High HLA-G expression is correlated with poor prognosis.
• HLA-G expression is passively correlated with the density of NK cells.
• HLA-G suppresses NK cell proliferation, cytotoxic reactions and cytokine production in vitro.
• HLA-G suppresses the anti-tumor effects of NK cells in vivo.

From the data, we learn that the HLA-G acts as an inhibitory ligand for KIR2DL4. 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.1 The timeline of Next-IOᵀᴹ programs.

Collaboration

Creative Biolabs is looking for potential partners and collaboration opportunities to co-develop anti-HLA-G 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.

For Research Use Only | Not For Clinical Use