Cytotoxic effect of immunotoxins in 2D and 3D models of sarcoma

Sarcomas are one of the most common types of cancer in children and comprise more than 50 heterogeneous histotypes. The standard therapeutic regimen, which includes surgery, chemotherapy and radiotherapy, does not often prove to be decisive. To improve patient outcome, alternative therapeutic strategies are being evaluated. Among these, RIP-containing immunotoxins (ITs) represent an innovative approach because of their high tumor specificity and cytotoxicity. Recently, in order to evaluate the efficacy of new drugs and develop personalized therapeutic protocols, three-dimensional models (i.e. spheroids and organoids) are emerging as valid tools in cancer research. My PhD project aimed to evaluate the cytotoxic effect of specific ITs, Tf-SO6, αEGFR1-Ocy and αHer2-Ocy, directed against TfR1, EGFR1 and Her2, in 2D (adherent cells) and 3D models (spheroids and organoids) of sarcoma. The results obtained showed that TfR1, EGFR1 and Her2 are highly expressed in our sarcoma models, and could be a possible target for immunotherapy. All tested ITs showed high specific cytotoxicity in 2D and 3D models, with IC50 values in nM range. Caspase 3/7 are highly activated after IT treatments in all cell models, but with different timing.