THERAPY-DEPENDENT INDUCTION OF SYSTEMIC ANTICANCER IMMUNE RESPONSE BY NANOTHERAPEUTICS
Prof. B. Rihova
Inst. of Macromolecular Chemistry,
AS CR, 162 06 Prague,
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.