The goals of this application are to evaluate the toxicities and immunogenicity of intravenous administration of dendritic cells (DC) pulsed with tumor antigen MART-1/gp 100 peptides as vaccines in patients with metastatic melanoma using anti-tumor immune responses as a surrogate marker, and regression of measurable tumor as a direct but secondary endpoint. These studies are based upon the hypothesis that immunization of melanoma patients with dendritic cells pulsed with a peptide corresponding to a class I MHC restricted tumor antigen epitope recognized by cytolytic T cells will augment the T cell immune response against their malignancy. The applicant will perform a Phase I study to define the toxicities of the DC vaccine approach in HLA-A2 melanoma patients with metastatic disease. At the conclusion of this study, he will then compare the immune responses to two selected doses of DC vaccine in a Phase Ib study with an expanded cohort number of up to 12 patients for each of two DC doses in order to more accurately define an optimum biologic dose of DC vaccine, which may not be the same as the maximal tolerated dose. Immune response will be assessed by proliferation of PBMC, lytic activity and cytokine release of bulk cytolytic T cells, and T cell limiting dilution analyses prior to and after vaccination. By testing different peptides to pulse DC for therapy of metastatic melanoma, he hopes to evaluate the overall concept of using peptide pulsed dendritic cells as a vaccine or as a priming maneuver to grow expanded antigen specific CTL for adoptive transfer.
| Lau, R; Wang, F; Jeffery, G et al. (2001) Phase I trial of intravenous peptide-pulsed dendritic cells in patients with metastatic melanoma. J Immunother 24:66-78 |
