DENDRITIC CELL VACCINES GENERATED FROM NAÏVE OR BREAST CANCER-BEARING MICE ARE PHENOTYPICALLY SIMILAR

NICOLA CANDIA, ALEJANDRO J.; ABT, ARACELI A.; ASAD, ANTONELA S.; ZUCCATO, CAMILA; IMSEN, MERCEDES; SAGRIPANTI, SOFIA; BAL DE KIER JOFFÉ, ELISA; ZANETTI, FLAVIA A.; SEILICOVICH, ADRIANA; CANDOLFI, M

Congreso; Reunión conjunta de sociedades de biociencias; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2018

The use ofdendritic cells (DCs) for antitumor immunotherapy has been widely studied inpreclinical and clinical settings showing good safety profiles. Although thesestrategies exert robust antitumor effects in preclinical cancer models,clinical efficacy has been lower than anticipated. This discrepancy could relyin part in the fact that DC precursors are extracted from cancer patients togenerate autologous vaccines, while in preclinical studies antitumor vaccinesare commonly generated from DC precursors from healthy animals. Consideringthat there is discrepancy on the functionality of CDs collected from cancerpatients, we aimed to characterize DCs cultured from the bone marrow of naïveand breast tumor-bearing mice. In order to optimize the culture conditions, wefirst evaluated the yield and purity of bone marrow cultures from naïve Balb/cmice grown for 7 days in medium supplemented with recombinant GM-CSF (rGM-CSF, 10ng/ml) or 30% conditioned medium (CM) from GM-CSF-producing mouse B myeloma J558 cell cultures. Thenumber of DCs obtained from these cultures was significantly higher whenprecursors were grown in J558 CM (2.1-3.0x106/mouse with 95% CD11c+cells) than in rGM-CSF (0.6-1.8x106/mouse with 55% CD11c+cells). We next characterized bone marrow cultures obtained fromimmunocompetent Balb/c naïve mice or mice bearing s.c. LM3 murine breastcarcinomas. Cells were grown for 7 days in J558 CM, exhibiting similar yieldbetween naïve (1.3-7.6 x106/mouse) vs tumor-bearing mouse bonemarrow (0.6-5.0 x106/mouse). DCs from naïve or tumor bearing mice werethen incubated with TLR9 agonist CpG1826 (10 µg/ml) and theiractivation status was assessed 48h later. Both cohorts of DCs exhibited comparablelevels of IL-12 and IL-10 secretion, as assessed by ELISA, as well as MHCII andCD86 expression, as determined by flow cytometry. Our results suggest that DCprecursors obtained from tumor-bearing mice retain the features of their normalcounterparts.