Abstract A24: Antigen-targeted soluble bispecific T-cell receptor (ImmTACTM) molecules in immunotherapy

Abstract

Abstract Cancer immunotherapies function to harness the body’s own immune system to eradicate cancer cells. Critical to this process is the T cell, capable of directing potent and antigen-specific immune responses. T-cell receptor (TCR) antigens are short intracellularly processed peptides presented on the cell surface. As the majority of the proteome is processed and presented on the surface of cells and hence can be targeted by a TCR, TCR-based therapies offer distinct advantages over antibody-based therapies that are limited to targeting only secreted or cell surface proteins. In this study, we describe our approach to address the limitations and utilize the natural advantages of the human TCR to target a diverse range of tumor indications. Immune mobilizing monoclonal TCRs Against Cancer (ImmTAC) molecules are a novel class of bispecific biologic formed from an affinity-engineered, soluble, targeted TCR fused to a T cell redirecting anti-CD3 scFv. We describe our process to engineer high-affinity ImmTAC molecules towards novel cancer antigens that have been identified and validated in house. Additionally, we discuss the challenges and opportunities in the preclinical testing of an exquisitely human-specific biologic that led to the development of an entirely in vitro preclinical package that is proven to support the clinical development of ImmTAC molecules to clinical development. In summary, we present a novel approach to cancer immunotherapy, detailing the engineering, optimization, preclinical testing and clinical development of ImmTAC molecules, a new bispecific biologic. Note: This abstract was not presented at the conference. Citation Format: Annelise Vuidepot. Antigen-targeted soluble bispecific T-cell receptor (ImmTACTM) molecules in immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A24.