TUMOR-TARGETED RELEASE OF IMMUNOSTIMULATORY AGENTS: SYNTHESIS AND BIOLOGICAL EVALUATION OF IMIDAZOQUINOLINE-BASED PRODRUGS AND ANTIBODY CONJUGATES

Different strategies have been proposed in order to achieve the targeted delivery of anticancer agents at the tumor site. Amongst the different delivery vehicles proposed, antibody drug conjugates (ADCs) have been especially successful in the clinic. Recently, the involvement of the immune system in cancer treatment has been exploited. Following this strategy, immune-stimulating antibody conjugates (ISACs) have emerged as a new class of ADCs which antitumor immune responses through the use of immunostimulatory drugs connected to monoclonal antibodies (mAbs) which serve as targeting units. Even though ISACs have already entered early phase clinical trials, they have demonstrated several drawbacks. In this thesis, the problems showed by 1st generation ISACs are tackled using diverse approaches, involving all parts of this class of constructs, from the antibody and linker design to the payload diversification