Intratumoral injection of bone-marrow derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas.

MELERO I; DUARTE M; RUIZ J; SANGRO B; GALOFRE JC; MAZZOLINI G; BUSTOS M; QIAN C; PRIETO J

GENE THERAPY

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 1999 p. 1779 - 1784

0969-7128

Stimulation of the antitumor immune response by dendritic required. The antitumor effect was inhibited by in vivo cells (DC) is critically dependent on their tightly regulated depletion of CD8+ T cells and completely abrogated by simability to produce interleukin-12 (IL-12). To enhance this ultaneous depletion with anti-CD4 and anti-CD8 mAbs. effect artificially, bone marrow (BM)-derived DC were gen- Mice which had undergone tumor regression remained etically engineered to produce high levels of functional IL- immune to a rechallenge with tumor cells, showing the 12 by ex vivo infection with a recombinant defective aden- achievement of long-lasting systemic immunity that also ovirus (AdCMVIL-12). DC-expressing IL-12 injected into was able to reject simultaneously induced concomitant the malignant tissue eradicated 50?100% well established untreated tumors. Tumor regression was associated with malignant nodules derived from the injection of two murine a detectable CTL response directed against tumor-specific colon adenocarcinoma cell lines. Successful therapy was antigens probably captured by DC artificially released dependent on IL-12 transfection and was mediated only by inside tumor nodules. Our results open the possibility of syngeneic, but not allogeneic BM-derived DC, indicating similarly treating the corresponding human malignancies.