Intratumoral injection of IL-secreting syngeneic/allogeneic fibroblasts transfected with DNA from breast cancer cells prolongs the survival of mice with intracerebral breast cancer.
Prior studies have revealed the immunotherapeutic properties of a vaccine prepared by transfer of genomic DNA from breast cancer cells into a highly immunogenic cell line. The rationale for this type of vaccine is that genes specifying an array of weakly immunogenic, unique tumor antigens associated with the malignant cells will be expressed in a highly immunogenic form by the transfected cells. Here, the immunotherapeutic properties of a vaccine prepared by transfection of mouse fibroblasts with DNA from a breast carcinoma (SB-5b) that arose spontaneously in a C3H/He mouse (H-2Kb) were tested in mice with intracerebral breast cancer. To augment their nonspecific immunogenic properties, before DNA transfer, the fibroblasts (of C3H/He mouse origin) were modified to express allogeneic MHC class I H-2Kb-determinants and to secrete IL-2, IL-18 or GM-CSF. The results indicate that C3H/He mice injected intracerebrally (i.c.) with the breast cancer cells and syngeneic/allogeneic-transfected fibroblasts modified to secrete IL-2 survived significantly longer (P < .005) than mice in various control groups, including mice injected i.c. with the breast cancer cells alone. The immunotherapeutic properties of transfected fibroblasts modified to secrete IL-18 or GM-CSF were less efficacious. The results of two independent in vitro cytotoxicity assays indicate that systemic cellular antitumor immunity was generated in mice injected i.c. with the transfected cells, and the immunity was mediated predominantly by CD8+ T cells.
Lichtor
Terry
T
Department of Neurosurgery, Rush University Medical Center, John H Stroger Hospital of Cook County, Chicago, Illinois 60612, USA. Terry_Lichtor@rush.edu
Glick
Roberta P
RP
Lin
Henry
H
O-Sullivan
Insug
I
Cohen
Edward P
EP
D000818:Animals; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy; D019496:Cancer Vaccines / Q000235:genetics / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D005822:Genetic Vectors / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D006183:H-2 Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D019496:Cancer Vaccines; D004273:DNA, Neoplasm; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; D020382:Interleukin-18; D007376:Interleukin-2; D007378:Interleukins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor