Next-IO™ Anti-ICOS Monoclonal Antibody Program

About This Program

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:

• 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.
• ICOS agonist monoclonal antibodies (mAbs) have shown to potentiate the effect of inhibitory checkpoint blockade.
• 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.

Program Plan

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.

Collaboration

Creative Biolabs is looking for potential partners (including but not limited to major pharma or biotech firms) to develop anti- ICOS monoclonal antibody program together. Our scientists are dedicated to bringing years of valuable experience to our partner and enabling a meaningful partnership. By using this strategic collaboration, we wish to help both sides to proceed with IND and many stages of clinical trials.

If you are interested in our program, please feel free to contact us to learn more details about the cooperation. Looking forward to working with you in the near future.

References

• Soldevilla, M.M.; et al. ICOS costimulation at the tumor site in combination with CTLA-4 blockade therapy elicits strong tumor immunity. Mol Ther. 2019, 27(11): 1878-1891.
• Burlion, A.; et al. A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system. Oncoimmunology. 2019, 8(7): 1596005.
• Solinas, C.; et al. The rationale behind targeting the ICOS-ICOS ligand costimulatory pathway in cancer immunotherapy. ESMO Open. 2020, 5(1): e000544.