Interleukin-2 secretion by transduced and unselected BDL-2 lymphoma results in increased survival in mice with previously established disseminated disease.
The transfer and expression of cytokine genes into malignant cells to provide a more effective tumor response has shown promise. The majority of murine models in which tumor vaccination strategies have been tested have utilized selected and expanded clones of tumor cells, which is impractical clinically. In a model of murine B lineage lymphoma (BDL-2), we compared the effectiveness of tumor vaccines composed of a) a BDL-2 clone established by G-418 resistance following transduction with the LIL2SN retrovirus and screened for maximal IL-2 secretion, b) a syngeneic fibroblast line transduced with LIL2SN and screened for G-418 resistance and IL-2 expression, which was co-injected with the parental line, and c) a heterogeneous (unselected) population of BDL-2 cells transduced with the MFG/IL2 virus, reported to provide enhanced expression of cytokine genes and minimize the need for selection. Testing of splenocytes derived from vaccinated animals reveals that injections of BDL-2 expressing IL-2 results in an increased capacity of splenocytes to kill BDL-2 in vitro, compared to vaccination of BDL-2 alone or in combination with IL-2 secreting fibroblasts. We show that a vaccine composed of MFG/IL2 transduced, unselected BDL-2 cells is equivalent or superior to a clone derived from LIL2SN transduction in prolonging survival of animals with previously established tumor. These studies provide evidence that transduction of tumor with MFG based vectors without in vitro selection leads to expression of high levels of IL-2 and can impact the survival of animals with disseminated tumor.
Orchard
P J
PJ
Department of Pediatrics, University of Minnesota Hospital.
Katsanis
E
E
Boyer
M
M
May
C
C
McIvor
R S
RS
Blazar
B R
BR
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D015316:Genetic Therapy; D007376:Interleukin-2 / Q000378:metabolism*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured; D014611:Vaccination
D019496:Cancer Vaccines; D007376:Interleukin-2