Induction of antitumor immunity using bone marrow-generated dendritic cells.
We have previously shown that bone marrow-generated dendritic cells (DC) pulsed with a class I-restricted peptide are potent inducers of CD8+ CTL. In the present study we have investigated whether bone marrow-generated DC are capable of inducing antitumor immunity. We show that a single immunization with DC pulsed with OVA peptide was highly effective in eliciting a protective immune response against a challenge with tumor cells expressing the OVA gene (E.G7-OVA), more so than immunization with irradiated E.G7-OVA cells, OVA peptide-pulsed RMA-S cells, or free OVA peptide mixed with adjuvant. The addition of free OVA protein to day 4 or day 7 bone marrow cultures, but not to day 9 mature DC, was also effective in eliciting CTL and engendering antitumor immunity, but was less effective than peptide-pulsed DC. Induction of CTL and antitumor immunity by bone marrow-generated DC pulsed with the class I-restricted OVA peptide correlated with the expression of syngeneic MHC class II molecules on the DC. This and the fact that induction of tumor immunity was dependent on CD4+ T cells suggest that in vivo priming of CTL and induction of antitumor immunity by bone marrow-generated DC also require the presentation of MHC class II-restricted epitopes and activation of CD4+ T cells. This observation has potentially important implications to the use of peptide-pulsed DC in clinical immunotherapy.
Porgador
A
A
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Snyder
D
D
Gilboa
E
E
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001853:Bone Marrow / Q000276:immunology*; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013945:Thymoma / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D010047:Ovalbumin