ImmTACs: bi-specific TCR-based reagents for targeted cancer immunotherapy (VAC7P.1037)

Abstract

Abstract ImmTACs (immune mobilizing monoclonal T cell receptors against cancer) are a new class of soluble bi-specific reagent that exploit the natural antigen recognition pathway mediated by the T cell receptor (TCR). As TCRs recognise HLA-presented peptides, ImmTACs can access the larger pool of intracellular tumor antigens unavailable to antibody based therapies. ImmTACs target tumors via a soluble monocloncal TCR, engineered to recognise a given tumor associated peptide-HLA complex with exceptionally high sensitivity and specificity. Once bound to their target, ImmTACs redirect host polyclonal T cells via an anti-CD3 antibody fragment. In this way ImmTACs facilitate targeted T cell recognition of tumors leading to potent T cell activation and tumor cell killing, with the potential to break T cell tolerance. ImmTACs are specific for humans, thus efficacy, specificity and off target effects cannot be assessed in animal models. Using antigen positive tumor cells and HLA appropriate primary human cell lines representing a range of tissues, the in vitro pre-clinical package can be predictive of in vivo clinical observations. A first ImmTAC, IMCgp100, has entered phase I/IIa clinical trials for patients with advanced melanoma. The drug is well tolerated and many patients show tumor shrinkage after the first dose of ImmTAC with tumor shrinkage improving with each dose. Emerging data demonstrate durable partial responses in three patients and a complete response in a fourth patient.