MATRACs · Tumor acidosis targeted delivery of immunotherapy by Marker-Agnostic TumoR-Anchoring Chimeras

Cancer immunotherapy represents a groundbreaking advancement in oncology, leveraging the immune system to combat malignancies with enhanced specificity and reduced systemic toxicity compared to traditional therapies. However, despite significant progress, current immunotherapies face limitations, particularly in targCancer immunotherapy represents a groundbreaking advancement in oncology, leveraging the immune system to combat malignancies with enhanced specificity and reduced systemic toxicity compared to traditional therapies. However, despite significant progress, current immunotherapies face limitations, particularly in targeting tumors without identifiable antigenic signatures and avoiding immune-related adverse events. In my ERC project I will explore an innovative approach utilizing Marker-Agnostic TumoR-Anchoring Chimera (MATRAC) technology, designed to harness the universal acidic microenvironment of solid tumors for targeted delivery of immune-modulating therapies. MATRACs are engineered recombinant fusion proteins that combine a therapeutic payload with a pH-responsive anchoring mechanism, ensuring selective activation in acidic tumor sites while minimizing off-target effects. Preliminary studies demonstrate MATRACs' enhanced tumor localization, pH-selective membrane binding, and potent immune-stimulating effects, laying the groundwork for their development as a versatile platform for innate immune-mediated cytotoxicity, cytokine therapy, and T-cell engagement in various cancer models. This research aims to optimize MATRACs' therapeutic efficacy and safety, with comprehensive preclinical evaluations including pharmacokinetics, immunogenicity, and toxicity assessments. By addressing critical gaps in current cancer immunotherapy, MATRAC technology holds the potential to expand treatment options for a broader range of patients, particularly those with antigenically challenging tumors, while improving the precision and effectiveness of immune-based therapies.