This program aims to develop anti-ICOS therapeutic monoclonal antibody for immuno-oncology.
ICOS is an immune checkpoint expressed in activated T cells, which can oppose T cell activation and in-Treg suppressive activity. ICOS/ICOSL axis has a dual role in participating in both anti-tumor T cell response and pro-tumor response. Therefore, both antagonist and agonist antibodies might be of interests in using ICOS/ICOSL pathway for cancer treatment.
ICOS
Inducible co-stimulator (ICOS) is the third member of the CD28/CTLA-4 family. As is well known, CD28 and CTLA-4, as one of the T cell-specific cell-surface receptors, are important regulators of the immune system. ICOS is a homodimeric protein with only low levels of resting, naïve T cells. It specifically binds to its ligand (ICOS-L), also known as B7-related protein-1 (B7RP-1), which is constitutively expressed in B cells. Multiple studies have shown that:
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ICOS-mediated signaling contributes to the regulation of activated T cells and effector T cell functions, and the potency of ICOS is enhanced following its binding to ICOS-L.
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ICOS agonist monoclonal antibodies (mAbs) have shown to potentiate the effect of inhibitory checkpoint
blockade.
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Antagonistic anti-ICOS mAbs not only can inhibit lymphoid tumour cells expressing ICOS, but also dampen
immunosuppressive function of Tregs cells.
Anti-ICOS Antibody Research in Cancer
Anti-ICOS antibody is often used in combination with other immunology agents in the clinic settings to
improve antitumor effects. Here are the published data about ICOS as a potential target for cancer
immunotherapy.
• ICOS agonist potentiates CTLA-4 blockade therapy in a melanoma mouse model.
Fig.1 ICOS agonist potentiates CTLA-4 blockade therapy in a melanoma mouse model.1
• ICOS Agonistic treatment in combination with CTLA-4 blockade promotes antitumor immune response.
Fig.2 ICOS Agonistic treatment in combination with CTLA-4 blockade promotes antitumor immune response.1
• Impact of antagonistic anti-ICOS mAb on the growth of HuMice tumors.
Fig.3 Impact of antagonistic anti-ICOS mAb on the growth of HuMice tumors.2
Indication
Based on the published data, we learn that ICOS is highly expressed in advanced solid malignancies, including endometrial, breast, lung, pancreatic, and CRC. Therefore, we intend to develop multiple programs for different indications (not limited to one specific tumor), in which ICOS is highly expressed.
Fig.4 Biology of ICOS in the tumor microenvironment.3
Clinical Trials under Progress
In cancer treatment, both antagonist and agonist antibodies using the ICOS/ICOS-L pathway are of interest to us. Currently, multiple efforts have been put into the researches on this pathway. However, the data efficacy, safety, and combination strategies with anti-ICOS agonists or antagonists have not been specified.
Despite this, ICOS is still a compelling target for cancer immunotherapy. In an effort to optimally leverage ICOS–mediated immune response, the next generation of ICOS targeted therapies attempts to explore combined therapeutic trials with other immunomodulatory agents.
With our extensive experience in providing CRO services, we are confident in providing streamlined end-to-end program. We are committed to developing a complete program, which tailors to the needs of our partners, from antibody discovery, engineering, optimization, to pre-clinical studies. Periodic progress report will be delivered to our clients for effective, smooth and timely communication.
Fig.5 The timeline of Next-IOᵀᴹ programs.