New Approach Targeting Myeloid-Derived Suppressor Cells for Therapy of Mammary Carcinoma

摘要

ABSTRACT The current therapies against Breast Cancer are limited by the intrinsic genetic instability of the neoplastic cells that facilitates the instauration of multidrug resistance mechanisms and promotes tumor escape mechanisms by altering the surface molecules recognized by active and passive immunotherapies. To overcome these limitations with the current project we are seeking to target by the use of doxorubicin conjugated RNA aptamer not the evasive neoplastic cells but host derived tumor associated Myeloid derived suppressor cells that compose up to 50% of the tumor mass. These cells induce T cell anergy and suppression, promote and stabilize tumor vasculature and metastatic activity. We successfully generated two aptamers recognizing molecules expressed on these cells and we developed a method to conjugate and purify doxorubicin conjugated aptamer with the intention to use them in vivo.