Interleukin-3 in gene therapy of cancer.
Retroviral Jzen vectors were used to introduce cytokine genes into cell lines established from a "moderately immunogenic" FSAR and a "non-immunogenic" FSAN murine fibrosarcoma. The effects of cytokine gene expression on tumour behaviour and host responses have been studied in vitro and in vivo. In this paper we report that, in comparison to other cytokines, interleukin-3 (IL-3) was surprisingly effective at enhancing the immunogenicity of irradiated tumour cell vaccines as seen by the development of protective immunity to parental tumour growth. Protection was tumour-specific and spleen cells from immunized mice could adoptively transfer immunity causing established parental tumours to regress in SCID mice. IL-3 acted through paracrine and endocrine pathways to induce largely a granulocyte infiltrate into tumours and through an autocrine pathway to increase major histocompatibility complex class I expression on both tumour types and CD44 expression on one. IL-3 gene transfer is worth further investigation as a method for enhancing the efficacy of tumour cell vaccines, but our study emphasizes that cytokine gene transduction can lead to stimulation of autocrine as well as paracrine pathways and both might be important in the generation of specific anti-tumour responses. These effects need to be carefully considered if cytokine gene transfer is to be effectively used in cancer immunotherapy.
Department of Radiation Oncology and Jonsson Comprehensive Cancer Center, UCLA School of Medicine 90024-1714.
W H
WH
McBride
G D
GD
Dougherty
A E
AE
Wallis
J S
JS
Economou
C S
CS
Chiang
D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D005434:Flow Cytometry; D015870:Gene Expression; D015316:Genetic Therapy; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016219:Immunotherapy, Adoptive; D007377:Interleukin-3 / Q000235:genetics* / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D013154:Spleen / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D007377:Interleukin-3