B. Rihova

Prof. B. Rihova Inst. of Macromolecular Chemistry, AS CR, 162 06 Prague, Czech Republic

Abstract:

Nanotherapeutics with dual, i.e. cytostatic and immunomodulating activity are still rare and at the very beginning of their understanding.  We repeatedly reported a dual activity of N-2(hydroxypropyl)methacrylamide (HPMA)-based targeted doxorubicin and paclitaxel. The treatment regularly triggers systemic anticancer resistance that protects mice from a second cancer attack. Such  resistance is dose, time and immune system dependent. No cured mice were recorded in the cohort of nude mice suggesting a critical contribution of T-cell mediated response to the final outcome of the treatment. The Winn´s neutralization assay had proven involvement of CD8⁺tumor-specific CTL. Also, mice suffering from acute tumor responded to the therapy with polymer-bound doxorubicin much better than mice suffering from chronic tumor model. Conjugates based on HPMA represent a new generation of anticancer drugs with improved therapeutic potential, decreased side effects and the ability to stimulate therapy-dependent tumor-specific resistance.

Targeting multiple pathways and show the importance of site targeted prevention by the combination of compounds of different nature.