This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, T. S. Articles by Cohen, E. P. Search for Related Content PubMed PubMed Citation Articles by Kim, T. S. Articles by Cohen, E. P.

Interleukin-2-secreting Mouse Fibroblasts Transfected with Genomic DNA from Murine Melanoma Cells Prolong the Survival of Mice with Melanoma¹

Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois 60612

A retrovirus was used to introduce a provirus (pZipNeoSVIL-2) containing the gene for interleukin-2 (IL-2) along with a neo^r gene (confers resistance to G418) into LM cells, a mouse cell line expressing defined major histocompatibility complex class I antigens (H-2^k). After initial selection in growth medium containing G418, IL-2 secretion was confirmed, and the cells were then cotransfected with genomic DNA from B16F1 or B16F10 melanoma cells, along with DNA from a plasmid (pHyg) that confers resistance to hygromycin. After a second round of selection in growth medium containing sufficient quantities of hygromycin to kill 100% of nontransfected cells but without further modification, the unfractionated populations of transfected cells were tested for their immunotherapeutic properties in C57BL/6 mice (H-2^b) with established B16 melanomas (H-2^b). Animals with melanomas treated with either of the transfected cell populations survived significantly (P < 0.01) longer than untreated mice or mice treated with irradiated (5000 rads) B16F1 melanoma cells. The animals also survived longer (P < 0.05) than mice with melanoma treated with IL-2-secreting LM cells transfected with genomic DNA from MOPC-315 cells, a nonimmunologically cross-reactive murine tumor. As determined by the capacity of monoclonal antibodies to T-cell subsets to inhibit the antimelanoma resonse in a ⁵¹Cr release assay, the antimelanoma immunity in mice immunized with cells transfected with genomic DNA from either B16F1 or B16F10 cells was mediated primarily by Lyt-2.2⁺ T-cells. These data raise the possibility that a generic, live cell tumor vaccine can be developed that can be modified to provide specificity for the neoplasms of individual patients.

¹ Supported by HHS Grant RO1 CA55651-02.

² To whom requests for reprints should be addressed, at the Department of Microbiology and Immunology (m/c 790), University of Illinois, E-703 Medical Science Building, 901 South Wolcott Avenue, Chicago, IL 60612-7344.

Received 12/20/93. Accepted 4/ 5/94.

This article has been cited by other articles:

				S. Todryk, A. A. Melcher, N. Hardwick, E. Linardakis, A. Bateman, M. P. Colombo, A. Stoppacciaro, and R. G. Vile Heat Shock Protein 70 Induced During Tumor Cell Killing Induces Th1 Cytokines and Targets Immature Dendritic Cell Precursors to Enhance Antigen Uptake J. Immunol., August 1, 1999; 163(3): 1398 - 1408. [Abstract] [Full Text] [PDF]

				E. F. de Zoeten, V. Carr-Brendel, and E. P. Cohen Resistance to Melanoma in Mice Immunized with Semiallogeneic Fibroblasts Transfected with DNA from Mouse Melanoma Cells J. Immunol., March 15, 1998; 160(6): 2915 - 2922. [Abstract] [Full Text] [PDF]