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Divisions of Surgical Oncology [A. R., L. H. B., L. A. B., C. M. V., R. L., V. B. D., B. H., A. Y. C., J. S. E.], Experimental Radiation Oncology [W. H. M.], and Hematology-Oncology [S. M. J., J. A. G.], University of California Los Angeles Medical Center, Los Angeles, California 90024
Dendritic cells (DCs) are professional antigen-presenting cells that process and present antigenic peptides and are capable of generating potent T-cell immunity. A murine tumor model was developed to evaluate methods of genetic immunization to the human MART-1/Melan-A (MART-1) melanoma antigen. A poorly immunogenic murine fibrosarcoma line (NFSA) was stably transfected with the MART-1 gene. This transfected tumor [NFSA(MART1)] grows progressively in C3Hf/Kam/Sed (H-2k) mice. Partial protection against a challenge with NFSA-(MART1) could be achieved with i.m. injections of a MART-1 expression plasmid or with systemic administration of an adenovirus vector expressing MART-1. However, superior protection was achieved when granulocyte macrophage colony-stimulating factor/interleukin-4-differentiated murine DCs transduced with an adenovirus vector expressing MART-1 were used for immunization. Both partial and complete protection could be achieved with i.v. administration of MART-1-engineered DCs. Splenocytes from immunized mice contained MHC class I-restricted CTLs specific for MART-1. This preclinical model of genetic immunization supports a therapeutic strategy for human melanoma.
1 Supported in part by NIH/National Cancer Institute Grant PO1CA5926-04 and the Monkarsh, Kesselman, and Minor Funds. A. R. was supported by a fellowship from the Fondo de Investigacion Sanitaria 95/5116. L. A. B. is a Howard Hughes Medical Institute Student Research Training Fellow.
2 To whom requests for reprints should be addressed, at Division of Surgical Oncology, Room 54–140 CHS. University of California Los Angeles School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90024-1782. Phone: (310) 825-2644; Fax: (310) 825-7575; E-mail: jeconomo@surgery.medsch.ucla.edu.
Received 4/ 7/97. Accepted 5/28/97.
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