Enhanced immunity to intracerebral breast cancer in mice immunized with a cDNA-based vaccine enriched for immunotherapeutic cells.
Structural differences between malignant and nonmalignant cells of the same individual form the basis of clinical immunotherapeutic strategies. Previously, we reported the therapeutic properties of a vaccine prepared by transfer of a cDNA-expression library from breast cancer cells into a highly immunogenic allogeneic fibroblast cell line where genes specifying an array of breast cancer antigens were expressed. Here, we report the application of this cell-based vaccination strategy for breast cancer metastatic to the brain. As relatively few cells in the vaccine were expected to have incorporated cDNA fragments specifying breast cancer antigens (most specify normal cellular constituents), an enrichment strategy was employed to increase the proportion of immunotherapeutic cells. Enhanced immunity to the neoplasm mediated predominantly by CD4+, CD8+, and NK/LAK cells was generated in the spleens of mice injected intracerebrally into the tumor bed with cells from the enriched vaccine, which translated into prolonged survival. Regulatory T cells (CD4+CD25+Foxp3+-positive) were relatively deficient in the spleen cells from tumor-bearing mice injected intracerebrally with the enriched vaccine.
D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D001932:Brain Neoplasms / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D001943:Breast Neoplasms / Q000473:pathology*; D015704:CD4 Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D051858:Forkhead Transcription Factors / Q000032:analysis; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D014162:Transfection; D016896:Treatment Outcome
D015704:CD4 Antigens; D019496:Cancer Vaccines; D018076:DNA, Complementary; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007376:Interleukin-2; D007371:Interferon-gamma