Independent cell types are involved in the induction of antimelanoma responses in C57BL/6 mice immunized with interleukin-2-secreting allogeneic mouse fibroblasts expressing melanoma-associated antigens

Tae Sung Kim, Mary K L Collins, Edward P. Cohen

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5 Citations (Scopus)

Abstract

Cellular antimelanoma immune responses developed during the coincubation of spleen cells from naive C57BL/6 mice (H-2<sup>b</sup>) with LM mouse fibroblasts (H-2<sup>k</sup>) genetically modified to express melanoma-associated antigens (MAA) and to secrete interleukin (IL)-2 (RLBA-IL-2 cells). Antimelanoma responses also developed following coincubation of spleen cells from naive mice with allogeneic cells (H-2<sup>k</sup>) that expressed MAA, but did not secrete IL-2 (RLBA-ZipNeo cells), or allogeneic cells (H-2<sup>k</sup>) that secreted IL-2, but did not form MAA (LM-IL-2 cells). However, in these instances, the magnitude of the responses was significantly less (p<0.01) than followed coincubation of spleen cells with the allogeneic cell construct (RLBA-IL-2) that combined IL-2 secretion with the expression of MAA. LM(TK-) cells (H-2<sup>k</sup>) or B16 cells (H-2<sup>b</sup>) failed to generate antimelanoma immune responses in populations of spleen cells from C57BL/6 mice. The cell types involved in the induction of the antimelanoma response by the genetically modified cells were determined by prior depletion of T-cell subsets with monoclonal antibodies before the addition of the cellular immunogens. Antimelanoma responses failed to develop in spleen cell populations depleted of T-helper cells if the cellular immunogen was non-IL-2 secreting (RLBA-ZipNeo cells). Prior depletion of T-helper cells did not affect the induction of an antimelanoma response in cell populations coincubated with constructs (RLBA-IL-2 or LMIL- 2) modified to secrete IL-2. The role of macrophages in the induction of the antimelanoma response was indicated by failure of macrophage-depleted populations to develop responses following coincubation with IL-2-secreting or nonsecreting cell constructs.

Original languageEnglish
Pages (from-to)298-304
Number of pages7
JournalJournal of Immunotherapy
Volume14
Issue number4
Publication statusPublished - 1993
Externally publishedYes

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Keywords

  • Allogeneic major histocompatibility complex
  • Gene transfer
  • Interleukin-2

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Immunology and Allergy
  • Pharmacology

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