Abstract 3527: Potent anti-tumor activity of AbGn-100, an anti-CD326 x anti-TCR bispecific antibody to CD326-expressing solid tumors

Abstract

Abstract CD326 is one of the first and prominent immunotherapeutic targets in cancer therapy due to its frequent and high-level expression on most carcinomas of various origins. The dominant role of cytotoxic T cells for tumor suppression and surveillance in vivo is well documented in literature. A novel bi-specific antibody AbGn-100 was constructed, in which the antigen-binding domain of an anti- human CD326 antibody was linked to the antigen-binding domain of an anti-human T cell receptor (TCR) ≤ chain antibody. Human serum albumin was incorporated into this construct to prolong the half life in vivo. This bi-specific antibody is able to direct T cells toward CD326-expressing cancer cells to execute T cell cytotoxic function after TCR cross-linking mediated by CD326 expressed on cancer cells while it remains harmless when either T cells or CD326-expressing cancer cells is absent. In vitro cytotoxicity assays with PBMCs from different donors have demonstrated potent (up to 60% above the background) cytotoxicity eliciting activity of AbGn-100 to lung (NCI-H358), ovarian (OMC3) and colorectal (COLO205) cancer cells lines. In the absence of cancer cells, the addition of AbGn-100 didn't trigger the up-regulation of T cell activation markers such as CD25 or CD69, nor did it increase the secretion of cytokines such as IL-2 and Interferon β, demonstrating the safety profile of AbGn-100. In vivo activity of AbGn-100 was tested with established lung (NCI-H358) and ovarian (OMC-3) cancer xenografts in NOD-SCID mice. AbGn-100, in the presence of human PBMC, significantly reduced the size of the established lung and ovarian tumors. Most notably, in some of the mice, tumor was not detectable after 50 days of treatment, suggesting the possibility of tumor eradication. PK studies in mice showed the half-life of AbGn-100 to be around 20 hours, which is substantially longer than conventional single-chain Fv bi-specific antibodies. These data support the potential of further development of AbGn-100 as therapeutics for the treatment of CD326-expressing solid tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3527. doi:1538-7445.AM2012-3527