Next-IO™ MHC I:LILRB2 Axis Therapeutic Monoclonal Antibody Program

About This Program

This program aims to develop anti-LILRB2 therapeutic monoclonal antibody for lung carcinoma immunotherapy.

Exciting advances in the field of cancer immunotherapy have driven basic research into immunomodulation in adaptive cell lineages and innate cell lineages. Studies have shown that:

• The immune clearance of cancer cells is regulated by a combination of phagocytosis and multiple anti-cell phagocytic signals - the "Don't Eat Me" signal. Modulating macrophage phagocytosis by blocking these inhibitory "don't eat me" signals is a potentially effective therapeutic strategy for cancer therapy.
• Cancer cells express the major histocompatibility complexes (MHC) class I to protect them from phagocytosis. This protective mechanism is mediated by the inhibitory receptor LILRB1, whose expression is upregulated on the surface of macrophages, including tumor-associated macrophages.

Given the above, blocking the MHC I-LILRB1 signal axis may be a potential strategy for anti-cancer immunotherapy.

MHC I:LILRB2 Axis

With the discovery of the "Don't Eat Me" CD47 molecule, antibody drugs based on the CD47-SIRPα signaling pathway have achieved amazing functions by targeting inhibitory macrophage-associated innate immune signaling pathways. The second "Don't Eat Me" molecule on tumor cells, named beta 2 microglobulin (β2m), a component of MHC class I. MHC class I and β2m, which are highly expressed on the surface of tumor cells, are combined with the leukocyte immunoglobulin-like receptor family B (LILRB1) on macrophages to send a "don't eat me" signal, resulting in loss of immune surveillance.

Fig.1 Identification of MHC class I as a "Don't Eat Me" molecule. (Zhao, 2019)

MHC class I molecules was newly identified as the second "Don't Eat Me" molecule in 2018. We wish to develop a rational and effective immunotherapy program and work with our partners to achieve precise tumor treatment based on the MHC I:LILRB2 axis.

Supporting Data

• LILRB2 blockade showed promising anti-tumor effects in the LLC tumor model.



• Tumor-infiltrating myeloid cells derived from lung cancer respond to LILRB2 blockade.

(Chen, 2018)

These data support the rationale for the development of the first-in-class human anti-MHC I:LILRB2 axis with an improved therapeutic index for the treatment of lung carcinoma.

Lung Cancer

• Lung cancer is one of the most common malignancies in humans. Currently, only 15% of lung cancer cases are diagnosed, and the remaining undiagnosed cancer cases develop into more aggressive forms, which reduces the 5-year survival rate of these patients to only 4%.
• The global lung cancer drug market size estimate for 2016 is $193 million, and the compound annual growth rate is expected to be close to 17% between 2016 and 2021.



• The global non-small cell lung cancer therapeutics market share, by therapy.

Ongoing Clinical Trials

• Currently, NO anti-MHC I:LILRB2 axis therapeutic antibodies have been evaluated in clinical trials. Our program will be a pioneer.
• We believe that this second "Don't Eat Me" targeting strategy will provide a “Plan B” for tumor immunotherapy, especially in the treatment of lung cancer. In an effort to optimally leverage MHC I:LILRB2-mediated immune response, our next-IO™ MHC I:LILRB2 axis targeted antibody program attempts to explore the optimal combination therapy trials by involving other immunomodulatory agents, particularly immune checkpoints.

Program Plan

We have extensive knowledge of end-to-end program development. For each program, we are committed to delivering the final complete program to our clients within 1.5 years before entering the IND stage.

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop LILRB2 therapeutic monoclonal antibody program together. Our scientists are dedicated to bringing years of valuable experience to our partner and achieve a meaningful partnership together. For any partners interested in our Next-IO™ programs, Creative Biolabs welcomes collaboration.

Here are two ways for your choice, and please contact us for more details.

1) Collaborate with us and co-develop the programs from the discovery phase to IND enabling. Costs will be shared.

2) Become a licensed candidate for our programs.

With our quality control protocol and knowledge of global regulatory requirements, we can help our partners further their programs with more chances to succeed. Look forward to cooperating with you in the near future.

References

• Zhao, J.; et al. The MHC class I-LILRB1 signalling axis as a promising target in cancer therapy. Scandinavian journal of immunology. 2019, 90(5): e12804.
• Chen, H.M.; et al. Blocking immunoinhibitory receptor LILRB2 reprograms tumor-associated myeloid cells and promotes antitumor immunity. The Journal of clinical investigation. 2018, 128(12): 5647-5662.

For Research Use Only | Not For Clinical Use