ImmTAC: A Novel Platform of T-Cell Receptor-Based Soluble Bispecifics

Immune mobilizing monoclonal T-cell receptors Against Cancer (ImmTAC®) molecules are innovative immunotherapies designed to harness the body's immune system to fight cancer. They consist of a soluble affinity-enhanced T-cell receptor (TCR) as the targeting arm, covalently linked to an antibody fragment specific to CD3 as the effector arm, enabling T-cell redirection and cancer cell killing. TCRs can target the intracellular antigenic landscape via recognition of peptides presented by surface localized Human Leukocyte Antigen (HLA) proteins, unlocking a choice of targets that are specific to the tumor. The ImmTAC platform has been validated in the clinic with the approval of tebentafusp in 2022 for the treatment of metastatic uveal melanoma. It is the first TCR therapeutic and first soluble bispecific targeting a solid tumor to be approved for commercial use. Here, we describe the methods to produce soluble, affinity-enhanced TCRs and high-affinity ImmTAC molecules.