CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Both costimulation and the frequency of inoculation are important to reject a murine T lymphoma in an immunization schedule using irradiated whole tumor cells
Autor/es:
DI SCIULLO PAULA; HERSCHLIK LETICIA; GRAVISACO MARÍA JOSÉ; WALDNER CLAUDIA; MONGINI CLAUDIA
Reunión:
Congreso; Primer Congreso Frances Argentino de Inmunología; 2010
Resumen:
Following the evaluation of an anti-tumor cell vaccine we are testing different vaccination schedules for anti-tumoral response optimization. In parallel, we continuous to dilucidate the mechanisms of the immunological response. BALB/c mice were inoculated i.p. with murine T-cell lymphoma cells (LBC) transfected or not with CD40 and irradiated, or with PBS. An experimental group received 2 doses of cells with an interval of 7 days, whereas another group received a single dose. Mice were challenged 7 days after the last immunization with tumor cells i.p. Our results indicated survival rates from 70-100% for LBC.CD40, 55 to 70% for LBC both immunized with 2 doses, and 33% for LBC.CD40 (1 dose), while none of the mice receiving 1 dose of LBC rejected the tumor. Mice immunized with 2 doses showed a significant difference in survival respect to the challenged group (p< 0,0459) and both groups immunized with 1 dose (p< 0,0323). Specific cytotoxicity by Jam’s method was 16% for LBC.CD40 (2 d), 13% for LBC (2 d) and 7% for normal mice. Surprisingly, the specific cytotoxicity found in the group immunized with 1 dose of LBC.CD40 was 38 %. In order to study if the generated immune response involved a Th1-Th2 mechanism, the levels of IFN-γ and IL-4 were determined in the supernatant of splenocytes immunized. While there was not any difference among the groups for IL-4, there was an increment in IFN production in all the groups immunized: LBC.CD40 (2 d) 1671pg/ml, LBC.CD40 (1d) 947pg/ml, LBC (2d) 1229pg/ml and normal (34pg/ml). Besides, the percentage of cellular populations were homogenous for CD4, CD8, F4/80, B220, CD49b and Gr1 in spleen and peritoneal washing. Our results indicate that it is necessary immunization with 2 doses to achieve a high percentages of tumor rejection. A Th1 mechanism is evolved in the anti-tumor response. One dose is not sufficient to reject the tumor, although activate a great number of cytotoxic T-cells, this seems not to be the main mechanism in the rejection of the tumor. However, it is important to note that immunization with cells transfected with costimulatory molecules, even with one dose, provides some protection against tumor.