Abstract 1346: Immunotherapy against breast cancer based on Stat3 blockade

In this study our objectives were to study whether immunization with supernatants (SN) produced by Stat3-blocked cells induces an antitumor immune response and to explore the contribution of senescence phenotype in this response. For that purpose we used BC models of ErbB-2-positive, JIMT-1 and KPL-4 cells (human) and C4HD cells (murine), and of triple negative, MDA-MB231 cells (human) and 4T1 cell (murine). Knockdown of Stat3 with siRNA in these cells, induced senescence (assessed by acidic β-galactosidase staining). In human BC cells the senescent phenotype was accompanied by up-regulation of p21cip1 and downregulation of Rb expressions. In mouse BC cells we observed an increased expression of p16ink4a. In addition, simultaneous transfection with siRNAs targeting Stat3 and p16ink4a reverted the senescent phenotype. Then, we used a pre-clinical model in which we embedded the SN of C4HD cells in a slow-delivery depot as an adjuvant of a cellular immunotherapy. We immunized the animals with irradiated C4HD cells together with a depot containing lyophilized SN of C4HD cells transfected in vitro either with Stat3 siRNA (senescent) and Stat3 and p16ink4a siRNA (non-senescent), or a control siRNA. After 3 immunizations, with 15 d of interval between them, animals were challenged with C4HD tumor and tumor growth was monitored for 40 d. We observed that immunization with SN of cells with Stat3 siRNA decreased tumor growth vs. control siRNA group. Interestingly, there was no differe...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Immunology Source Type: research