Cytokine gene transfer as a therapeutic strategy.
Cytokine gene therapy for cancer could involve either the direct delivery of cytokine genes to established tumours to stimulate their rejection or the injection of cytokine-secreting tumour cells to stimulate an immune response that could reduce metastatic disease. To assess the feasibility of the first approach, we have compared the ability of different cytokine-secreting tumour cells to induce the rejection of admixed, unmodified cells. While interleukin (IL)-2- or interleukin-4-secreting tumour cells were ineffective, interferon-gamma (IFN-gamma)-secreting cells could induce rejection of 10% admixed, unmodified cells. Because direct gene delivery to tumours is unlikely to be 100% efficient, these data suggest that IFN-gamma may be the most suitable of these cytokines for this approach. However, we have demonstrated that injection of IL-2-secreting tumour cells, following primary tumour excision, can prevent the development of metastases and prolong survival of rats. This suggests that IL-2-secreting tumour cells can be effective in the treatment of metastatic disease.
Patel
P M
PM
Section of Cell and Molecular Biology, Institute of Cancer Research & Royal Marsden Hospital, London, U.K.
Flemming
C L
CL
Russell
S J
SJ
Eccles
S A
SA
Collins
M K
MK
D000818:Animals; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D051381:Rats
D016207:Cytokines