Interleukin-2-secreting mouse fibroblasts transfected with genomic DNA from murine melanoma cells prolong the survival of mice with melanoma

Tae Sung Kim, Edward P. Cohen

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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-2b) with established B16 melanomas (H-2b). 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 response 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.

Original languageEnglish
Pages (from-to)2531-2535
Number of pages5
JournalCancer Research
Volume54
Issue number10
Publication statusPublished - 1994 May 15
Externally publishedYes

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Interleukin-2
Melanoma
Cell Survival
Fibroblasts
DNA
Proviruses
Histocompatibility Antigens Class I
Experimental Melanomas
Cancer Vaccines
T-Lymphocyte Subsets
Retroviridae
Growth
Major Histocompatibility Complex
Inbred C57BL Mouse
Population
Genes
Immunity
Neoplasms
Plasmids
Monoclonal Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Interleukin-2-secreting mouse fibroblasts transfected with genomic DNA from murine melanoma cells prolong the survival of mice with melanoma. / Kim, Tae Sung; Cohen, Edward P.

In: Cancer Research, Vol. 54, No. 10, 15.05.1994, p. 2531-2535.

Research output: Contribution to journalArticle

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