Description

IMCgp100: A new TCR-based protein therapeutic weapon in the battle against malignant melanoma

Dominic Sweeney, Luke Williams, Nathaniel Liddy, Giovanna Bossi, Jane Harper, Joseph Dukes, Samantha Paston, Frayne Bianchi, Tara Mahon, Malkit Sami, Emma Baston, Brian Cameron, Andrew Johnson, Namir Hassan, Annelise Vuidepot and Bent Jakobsen.

Immunocore Ltd, 101 Park Drive, Milton Park, Abingdon, OX14 4RY, UK

Efficient T cell-mediated clearing of cancer cells is limited by the ability of T cells to recognise tumour-associated antigens (TAAs). As T cells that express T cell receptors (TCRs) with a high affinity to self-antigens are deleted during immune system development, self-tolerance to TAAs is common. In order to overcome these limitations and harness the power of T cells in cancer therapeutics, Immunocore Ltd has developed ImmTAC^TM molecules (immune-mobilising monoclonal TCR against cancer). ImmTAC molecules have the ability to potently re-direct the immune system to destroy tumour cells in a specific manner.

ImmTAC molecules are bispecific biologics that consist of a high affinity monoclonal TCR covalently linked to a scFv antibody fragment specific to CD3, a TCR co-receptor present on the T cell surface. In our lead ImmTAC, IMCgp100, the TCR component has been engineered to possess picomolar affinity for the HLA-A2-associated peptide of gp100_280-288, a well-characterised melanoma-specific TAA. Extensive pre-clinical in vitro studies have shown that IMCgp100 specifically redirects T cells against melanoma targets expressing gp100 and HLA-A2. A first in human clinical study with IMCgp100 has demonstrated a favourable safety profile for the therapeutic. These clinical data also show durable tumour responses with evidence of immune cell activation observed in both cutaneous and uveal melanoma patients. The current clinical data suggests that the ImmTAC format is a promising new technology in the cancer immunotherapy field.