As a thriving global biologics company, Creative Biolabs has the initiative to acquire, develop, and commercialize Next-IO™ programs with a goal to treat cancers. We believe our advanced platforms and experienced scientists can help worldwide clientele take the front seat in immunotherapy pipelines. This anti-sMIC monoclonal antibody program aims to develop therapeutic mAb that could activate NK cell immune responses and attack cancer cells.
DNA damage, chromatin modulations, oncogene activation or oxidative stress are all hallmarks of cancer. These abnormities cause cellular distress by upregulating Stress-induced ligands and create damaged or transformed cells that support to be recognized and eliminated by the immune system. “Stress-induced ligands” are MHC I chain-related molecules A and B (MICA and MICB, generally termed MIC), which can be recognized by NKG2D (natural-killer group 2, member D) receptor expressed on NK cell and some other T cell subsets. The engagement of NKG2D by MIC triggers the immune system activation to eliminate the cancer cells. Studies have indicated soluble MIC derived from tumor cells has immunosuppressive effects. Therefore, targeting sMIC can be a potential therapeutic approach to treat cancer.
Fig.1 Engagement of NKG2D by MICA can trigger the NK cell cytotoxicity function.1
For some solid tumor cells that express high levels of MIC, it indicates a dominant immune evasion mechanism exists and tumor cells with a high level of MIC could ignore NKG2D-mediated immune responses. Clinical studies revealed that overexpressed soluble MIC (sMIC) is related to advanced forms of cancers and most sMI is produced in exosomes, or through ectodomain shedding that mediated by metalloproteases. sMIC is highly immunosuppressive and also able to downregulate NKG2D receptors, promote the expansion of myeloid suppression cells in the tumor microenvironment, disrupt NK cell maintenance, and inhibit macrophages activated phenotypes. All these findings endorse sMIC to be a potential immuno-therapeutic target. Our anti-sMIC antibody program is to develop the non-blocking sMIC-neutralizing antibody that could reverse the sMIC-induced immune suppression and improve its innate and adaptive immune responses.
Fig.2 Potential therapeutic interventions to target NKG2D ligand MIC for cancer immunotherapies.2
Fig.3 Anti-sMIC monoclonal antibody-B10G5 is highly effective against prostate carcinoma in the double transgenic TRAMP/MIC mice model.3
Fig.4 Anti-sMIC monoclonal antibody-B10G5 significantly enhance the rate of NK cell renewal.3
Fig.5 Anti-sMIC monoclonal antibody-B10G5 significantly enhance IFNγ production of NK cells.3
From the findings, we believe anti-sMIC antibody therapy can achieve effective tumor killing. For any additional assistance, please feel free to reach out to our scientists.
With extensive experience in the discovery and development of therapeutic antibodies, Creative Biolabs is dedicated to providing the top-notch Next-IO™ programs to our clients. We are committed to delivering the finalized program to our partners 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.6 The timeline of Next-IOᵀᴹ programs.
Creative Biolabs is excited to offer years of valuable contract research organization (CRO) experience to our programs our partners and achieve more strategic collaborations together. We have accumulated extensive experience during the years of operations in antibody discovery and development. We believe our collaboration will unleash the creative spirit and achieve greater success in immuno-oncology. Creative Biolabs welcomes proposals from clients if you are interested in co-developing programs in immuno-oncology.
If you are interested in the collaborations, please don’t hesitate to contact us to learn more.
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