Combination effect of vaccination with IL2 and IL4 cDNA transfected cells on the induction of a therapeutic immune response against Lewis lung carcinoma cells.
In order to develop a more effective method of immunotherapy we have transfected mouse interleukin-2 (IL2) or mouse interleukin-4 (IL4) cDNA into a spontaneous non-immunogenic murine lung cancer. Lewis lung carcinoma (LLC). IL2 cDNA transfection more strongly decreases tumorigenicity of LLC than IL4 cDNA transfection. Recombinant-human-IL2 treatment of mice that were transplanted with untransfected LLC could not prolong their survival. In contrast, vaccination with IL2-cDNA-transfected LLC (LLC-IL2) and LLC-IL2 mixed with IL4-cDNA-transfected LLC (LLC-IL4) could significantly suppress tumor growth of LLC in a tumor-specific manner. The vaccination with LLC-IL2 mixed with the same number of LLC-IL4 cells was more suppressive to the growth of LLC than that with LLC-IL2 cells alone, while LLC-IL4 vaccination alone was ineffective. Nude, severe-combined-immune-deficient (SCID) and beige mice were unable to reject LLC-IL2 cells. However, immunodeficient mice responded to LLC-IL2, but not to LLC, since their survival times after transplantation with LLC-IL2 cells were significantly longer than the survival time of normal or immunodeficient mice transplanted with untransfected LLC cells. We conclude that vaccination with IL2-producing tumors and, with more pronounced effect, in combination with IL4-producing tumors, is able to induce an immune response to this normally non-immunogenic tumor. Tumor rejection appears to be achieved by the combined activity of CTL and NK cells. This strategy has potential for new immunotherapeutic interventions in cancer patients.
Ohe
Y
Y
Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
Podack
E R
ER
Olsen
K J
KJ
Miyahara
Y
Y
Ohira
T
T
Miura
K
K
Nishio
K
K
Saijo
N
N
D000818:Animals; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D005260:Female; D007167:Immunotherapy; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008815:Mice, Inbred Strains; D016019:Survival Analysis; D014162:Transfection; D014611:Vaccination
D007376:Interleukin-2; D015847:Interleukin-4