Resumen
Due to the nonspecific nature of disease symptoms and late diagnosis, prognosis for ovarian cancer remains poor, while its incidence is increasing dramatically. Current treatment options lead to recurrence for over 80% of patients, and there is a real and urgent need to identify new therapeutic targets, especially in the field of immuno-oncology. Among possibilities, thrombospondin-1 (TSP-1) is a matricellular protein being overexpressed within ovarian tumors, for which interaction with CD47 receptor was reported as directly inhibiting adaptive immunity. We engineered the first-ever orthosteric antagonist that is selective for TSP-1:CD47 interaction, namely TAX2. TAX2 is a cyclic peptide targeting tumor-overexpressed thrombospondin-1 (TSP-1) to prevent CD47 receptor activation. TAX2 acts as a modulator of the tumor-tolerant microenvironment, reprogramming highly vascularized tumors into poorly angiogenic ones, while concomitantly activating the tumor-inhibiting immune system. A large body of in vivo efficacy data support the proof-of-concept for TAX2 use as an anti-cancer therapy.