Prolongation of the survival of breast cancer-bearing mice immunized with GM-CSF-secreting syngeneic/allogeneic fibroblasts transfected with a cDNA expression library from breast cancer cells.
Breast cancer cells, like other types of neoplastic cells, form weakly immunogenic tumor-associated antigens. The antigenic properties of the tumor-associated antigens can be enhanced if they are expressed by highly immunogenic cells. In this study, a cancer vaccine was prepared by transfer of a cDNA expression library from SB5b breast carcinoma into mouse fibroblast cells of C3H/He mouse origin (H-2(k)), that had been previously modified to secrete GM-CSF and to express allogeneic class I-determinants (H-2(b)). The transfected syngeneic/allogeneic fibroblasts secreting GM-CSF were used as a vaccine in C3H/He mice. Robust cell-mediated immunity toward the breast cancer cells was generated in mice immunized with the cDNA-based vaccine. The immunity, mediated predominantly by CD8(+) T lymphocytes, was directed toward the breast cancer cells, but not against either of two other non-cross-reactive neoplasms of C3H/He mice. The immunity was sufficient to prolong the survival of mice with established breast cancer. Among other advantages, preparation of the vaccine by cDNA-transfer into a fibroblast cell line enabled the recipient cells to be modified in advance of DNA-transfer to augment their immunogenic properties. As the transferred DNA is replicated as the transfected cells divide, the vaccine could be prepared from microgram quantities of tumor tissue.
Kim
Tae S
TS
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. tskim@korea.ac.kr
Jung
Mi Y
MY
Cho
Daeho
D
Cohen
Edward P
EP
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000401:mortality*; D016827:CD8 Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D018076:DNA, Complementary / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000166:cytology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014184:Transplantation, Homologous / Q000276:immunology; D014185:Transplantation, Isogeneic / Q000276:immunology
D016827:CD8 Antigens; D019496:Cancer Vaccines; D018076:DNA, Complementary; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor