Abstract 688: Anti-CNTN4 antibody, GENA-104A07 suppresses tumor growth in murine syngeneic tumor models by regulating T cell function

• Published in: Cancer research (Chicago, Ill.) Ill.), 2021-07, Vol.81 (13_Supplement), p.688-688
• Main Authors: Cha, Mi Young, Houh, Youn Kyung, Kim, Yun Yeon, Kim, Hyunuk, Chung, Joo-Yeon, Park, Kyung Mi, Park, Hansoo
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2021-688

Vast improvements in tumor treatment have been achieved with immune checkpoint inhibitors. They have been approved for use in monotherapy or combinations for patients with different types of cancer. However, the treatments often yield limited benefits and strong responses are observed only in a minority of treated patients. For this reason, enormous efforts have been made to explore primary or acquired resistance mechanisms to improve the available current therapies. CNTN4 (contactin 4, alias BIG-2) is a neuronal cell adhesion molecule, which is mainly expressed in the human brain and functions in axonal growth and guidance. Some genetic evidence has indicated that CNTN4 may be associated with non-neurological disorders such as cancer and cardiovascular conditions as well as neurodevelopmental disorders. Recently we identified CNTN4 as a novel immunomodulatory protein, which is expressed on tumors. In this study, we investigate the potential of CNTN4 as a cancer immunotherapeutic target, using GENA-104A07 to target it. GENA-104A07 is a humanized IgG4 monoclonal antibody that specifically binds to human and mouse CNTN4 with sub-nanomolar binding affinity by ELISA assay, not to any other related proteins having similar sequences. This molecule competitively interferes with the binding of CNTN4 and its receptor protein. The in vitro functional effect showed that the treatment of GENA-104A07 alleviates the immune suppressive effect induced by CNTN4 on T cells. Consequently, the administration of GENA-104A07 induces significant suppression of the tumor growth as monotherapy in syngeneic mouse models with a high expression level of CNTN4. GENA-104A07 treatment increases the expression of activation markers and pro-inflammatory cytokines on T cells. Taken together with in vitro and in vivo studies, the efficacy of GENA-104A07 demonstrated that CNTN4 blockage with monoclonal antibody may provide an immunotherapeutic strategy for human cancer. Currently, the preliminary safety study is ongoing in mice, and IND enabling studies will be initiated early next year with the optimized antibody. Citation Format: Mi Young Cha, Youn Kyung Houh, Yun Yeon Kim, Hyunuk Kim, Joo-Yeon Chung, Kyung Mi Park, Hansoo Park. Anti-CNTN4 antibody, GENA-104A07 suppresses tumor growth in murine syngeneic tumor models by regulating T cell function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA):