TUMOR PROTECTION OF MICE IMMUNIZED WITH TUMOR CELLS TRANSFECTED WITH TCR COSTIMULATORY MOLECULES

DE LUCA PAOLA; RUYBAL PAULA; GRAVISACO MARIA JOSE; WALDNER CLAUDIA; MONGINI CLAUDIA

Cordoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología; 2005

Previously we demonstrated that CD40L, CD40, or CD80 expression on LBC tumor cells (LBC.40L, LBC40 or LBC80) significantly decreases tumorigenicity when compared to parental LBC cells or mock transfected cells (LBC.Mock). The aim was to analyse if syngeneic mice immunized with irradiated LBC cells transfected with TcR costimulatory molecules would induce protection against parental LBC cells. BALB/c mice were inoculated once a week for three times with live, irradiated  LBC.40L, LBC40 or LBC80 cells following two different routes. Mice were immunized combining the subcutaneously (s.c) and intraperitoneal rout (i.p) with equal inoculums, or just s.c. Seven days after the last vaccination, mice were challenged. The percentage of tumor incidence (%TI) was calculated and the time at which 50% of challenged mice had died (DT50) was recorded. Mice immunized s.c. with transfected or not transfected LBC cells did not display a significant reduction neither in tumor incidence nor in the DT50 (p<0.005, log Rank Test). Table 1 shows the results obtained inoculating mice (n=12) by the s.c + i.p route . Inoculum Challenge DT50 s.c+i.p (days) % TI s.c+i.p LBCi 1x106 LBC 23 50 LBC.Mocki 1x106 LBC 24 50 LBC.CD40i 1x106 LBC 24 50 LBC.CD80i 1x106 LBC 43 50 LBC.CD40Li 1x106 LBC 32 50 PBS 1x106 LBC 17 0 Vaccination with irradiated LBC cells wether transfected or not conferred protection from challenge LBC cells. But when immunizating with LBC.CD80i and LBC.CD40Li the DT50 increased 20 and 9 days, respectively, when compared with mice inoculated with irradiated LBC. Our results demonstrated that immunization with LBC cells expressing CD80 or CD40L conferred protection against a challenge with parental tumor. The route of immunization is an important point to consider as mice immunized by s.c route did not displayed a significant protection while the combination of s.c and i.p route significantly enhanced the protection agaist tumor challenge.