대한대장항문학회

PURPOSE: Activated bone marrow-derived dendritic cells (DCs) express high level of MHC class I and II molecules as well as intercellular adhesion molecule and B7, required for T cell activation. This study was designed to examine whether DCs pulsed with<br>tumor lysates were capable of inducing tumor specific CTLs. METHODS: To generate mature DCs, bone marrow cells of female BALB/c mice were cultured in the presence of GM-CSF and IL-4. Mature DCs were idenfied by surface expression of MHC class II<br>molecules and costimulatory molecules. By FACS analysis, it was found that most DCs highly expressed B7-1, B-7-2 and CD40 as well as MHC class II molecules. BAlB/c were immunized subcutaneously. Cytolytic activity was determined by chromium release<br>assay using splenocytes harvested from immunized mice 7 days after the immunization, Cytolytic activity was measured against CT-26 and RAG tumor cells. In vivo protection experiment was performed. Mice were immunized subcutaneously wity DCs pulsed with<br>CT-26 lysates (1×10(6) per mouse) and were challenged intrahepatically with wild type CT-26 (5×10(4) per mouse) two weeks following immunization. Three weeks after the challenge, animals were euthanized for identification of hepatic tumors.<br>RESULTS:<br>Lysis of CT-26 cells were significantly greater with the splenocytes from the immunized mice. Incidence and mean volume of hepatic cancer in the immunized group were 50% (5/10) and 78+/-22 mm3. These results were significantly different from those from<br>control groups: 100% (10/10) and 1014.5+/-667.8 mm3 in media treated group, 90% (9/10) and 855.5+/-270.6 mm3 in mice treated with irradiated CT-26, 100% (10/10) and 994+/-255 mm3 in the animals treated with DC alone. CONCLUSIONS: DCs pulsed with CT-26<br>lysates could successfully induce antitumor immunity in the BLAB/c against syngeneic CT-26 carcinoma cells. Pulsing method was so simple that neither genetic engineerings nor cellular fusion were not necessary. Even though the present study did not<br>conduct survival experiments, it was thought that clinical application of DC-based immunotherapy could be expedited by pulsing of tumor lysate into the DCs.<br>