Next-IO™ Anti-IL-1/IL-1R Axis Targeted Therapeutic Antibody Program

About This Program

This program aims to develop anti-IL-1/IL-1R axis targeted therapeutic antibody for immuno-oncology.

Inflammation is an important component of the tumor microenvironment. The IL-1/IL-1R axis regulates the inflammatory cytokine signaling pathway and plays a key role in carcinogenesis and tumor progression. Studies have shown that IL-1 plays different roles in tumor initiation and progression, including driving chronic unresolved inflammation, tumor angiogenesis, activation of the IL-17 pathway, induction of bone marrow-derived suppressor cells (MDSC), and macrophage recruitment, invasion and transfer. This highlights a clear rationale for IL-1/IL-1R axis-based cancer immunotherapy.

IL-1/IL-1R Axis

In recent years, IL-1 has become a key cytokine involved in innate and adaptive immunity with new and unexpected prospects:

IL-1 is a key driver of congenital (ILC3) and adaptive (Th17) lymphocyte differentiation and therefore plays a role in the coordinated response of polarized lymphocytes.
IL-1 ligand gene expression is associated with poor prognosis and can induce expression of various tumor-promoting factors involved in immune cell recruitment and angiogenesis.
IL-1 signaling has been shown to play a role in tumor suppression through natural killer (NK) and T cell mediated cytotoxicity, which is also a major anti-tumor effect.

Fig.1 Functions of IL-1 signaling in cancer.¹

IL-1/IL-1R Axis in Cancer Studies

Here are some published data about IL-1/IL-1R work as a potential target for cancer immunotherapy.

IL-1R antagonist (Anakinra) controls the transcriptional signature of inflammation in metastatic breast cancer.

Fig.2 Kinetics of tumor growth from multiple experiments.²

IL-1α overexpression enhances the anti-tumor efficacy of cetuximab (CTX).

Fig.3 IL-1α overexpression enhances the anti-tumor efficacy of cetuximab.³

IL-1R blockade inhibits human breast cancer growth.

Fig.4 Growth curves and Kaplan–Meier survival curves of mice treated with or without IL-1Ra.⁴

Ongoing Clinical Trials

Currently, several anti- IL-1/IL-1R antibodies are currently being evaluated in clinical trials after successful testing in animal models. An increasing number of therapeutic molecules are getting confirmed on its role in immune responses and their early clinical trial data shows great promise. However, further studies are needed to optimize the efficacy, safety, and combination strategies to achieve greater clinical success.
In this case, IL-1/IL-1R axis is still a compelling target for cancer immunotherapy. In an effort to optimally leverage IL-1-mediated immune response, our next generation of IL-1/IL-1R axis targeted treatment attempts to explore combination therapy trials with other immunomodulatory agents.

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 prior to entering the IND stage.

Fig.5 Project pipeline management of therapeutic monoclonal antibody.

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop anti-IL-1/IL-1R axis targeted therapeutic antibody program together. Our scientists are dedicated to bringing together years of valuable experience to our partner and achieve a meaningful partnership. For commercial 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 and their programs enter the market faster. Look forward to working with you in the near future.

References

Kavin, J.; et al. IL-1 Family Members in Cancer; Two Sides to Every Story. Front. Immunol. 2019,10:1197.
Wu, T C.; et al. IL1 receptor antagonist controls transcriptional signature of inflammation in patients with metastatic breast cancer. Cancer research. 2018, 78(18): 5243-5258.
Espinosa-Cotton, M.; et al. Interleukin-1 alpha increases anti-tumor efficacy of cetuximab in head and neck squamous cell carcinoma. Journal for immunotherapy of cancer. 2019, 7 (1): 1-16.
Guo, B.; et al. Targeting inflammasome/IL-1 pathways for cancer immunotherapy. Scientific Reports. 2016,6:36107.

For Research Use Only | Not For Clinical Use