Definition

An antibody-drug conjugate (ADC) composed of HT-19, a monoclonal antibody directed against the tumor-associated antigen (TAA) human epidermal growth factor receptor 2 (EGFR2; HER2; ErbB2), linked to a payload composed of an agonist for the stimulator of interferon genes protein (STING; transmembrane protein 173; TMEM173), with potential immuno-activating and antineoplastic activities. Upon intravenous administration of anti-HER2 STING agonist ADC XMT-2056, the anti-HER2 antibody moiety targets and binds to HER2 while the STING agonist targets and binds to STING on immune cells in the tumor microenvironment (TME). This allows for specific activation of the STING pathway in the TME. This leads to the production of pro-inflammatory cytokines, including interferons (IFNs), enhances the cross-presentation of tumor-associated antigens (TAAs) by dendritic cells (DCs), and induces a cytotoxic T lymphocyte (CTL)-mediated immune response against cancer cells. STING, a transmembrane protein that activates immune cells in the TME, plays a key role in the activation of the innate immune system. The conjugation of the anti-HER2 antibody to the STING agonist improves targeted delivery of the STING agonist and increases tumor exposure and enhances the STING-mediated anti-tumor immune responses while limiting systemic toxicity.