Abstract 6335: Developing anti-IL-22 therapeutics for inflammation and cancer

Abstract Chronic inflammation facilitates the development of cancer, age-related, inflammatory autoimmune and other diseases. Proinflammatory cytokines play a central role in this pathogenic process by driving activation of NF-ƙB, STAT3 and other signaling cascades. IL-22 is an inflammatory cytokine involved in the pathology of autoimmune diseases such as psoriasis, atopic dermatitis, and ulcerative colitis. IL-22 has also been shown to promote epithelial cell proliferation, stemness and tumorigenesis in cancer. Recent studies demonstrated that neutralization of IL-22 reduced dysplasia and tumor development in preclinical models. To date, there has not been a clear application for anti-IL-22 therapy for autoimmune diseases and cancer, likely due to identifying the right disease indication and to their low potency and low efficacy. Thus, there remains an opportunity to explore the potential of more potent anti-IL-22 therapeutics. Using BioAtla’s proprietary antibody discovery and engineering platforms, we have generated humanized anti-IL-22 antibodies with high affinities to human, cynomolgus and mouse IL-22. In vitro data demonstrated that our anti-IL-22 antibodies inhibited IL-22-induced p-STAT3, CXCL-1 and IL-10 activities. In addition, our antibodies showed a 10-fold increased binding activity to human IL-22 compared to Fezakinumab, which was previously developed by Pfizer for the treatment of autoimmune diseases. BioAtla’s high affinity anti-IL-22 antibodies were shown to be more potent relative to Fezakinumab using multiple in vitro assays. To test the functions of our antibodies in vivo, we also established mouse models to determine anti-IL22 efficacy. More specifically, to study whether targeting IL-22 in an inflammation-induced tumor microenvironment reduces tumor occurrence, we developed an inflammation-driven sporadic colitis-associated colorectal cancer mouse model for ongoing cancer studies that will be discussed. In addition, we evaluated our anti-IL22 antibodies in an imiquimod-induced psoriasiform skin inflammation mouse model. The mice treated with potent anti-IL-22 antibodies had significantly reduced skin lesions, including erythema, scales, and skin thickness compared to isotype antibody-treated mice. Q-PCR analysis of the mouse skin demonstrated that treatment with our anti-IL-22 antibody led to significantly decreased RNA levels of the imiquimod-induced inflammatory marker CXCL3. Thus, the enhanced anti-IL-22 therapy is a promising strategy for targeting anti-inflammation in autoimmune diseases, such as psoriasis and atopic dermatitis, and inflammatory cancers, including colorectal cancer. In conclusion, the development of a potent, species cross reactive anti-IL-22 antibody using BioAtla’s antibody discovery and engineering platforms addresses the challenges of anti-IL-22 therapeutics and allows for translational studies in relevant animal efficacy and safety models. Citation Format: Christina Wheeler, Jian Chen, Cathy Chang, Gerhard Frey, Haizhen Liu, Jing Wang, Kathryn Woodard, Solmarie Joyner, Wei Zhou, William J. Boyle, Jay M. Short. Developing anti-IL-22 therapeutics for inflammation and cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6335.