Cytokine-mediated gene therapy for cancer.
BACKGROUND
Significant interest has been generated in the gene therapy of cancer. One strategy involves tumor-directed cytokine gene transfer and its effects on tumor immunobiology.


METHODS
The authors review the current literature pertaining to cytokine gene therapy of cancer and provide a description of gene transfer methods currently being evaluated.


RESULTS
Several cytokine gene transfer models have been described involving at least 12 different cytokines. The introduction of cytokine genes into experimental animal tumors improves their ability to be recognized and destroyed by the host immune system. Certain cytokines will regulate phenotypic properties such as major histocompatibility complex antigens, immunosuppressive peptides, protooncogenes or endogenous cytokine production. Cytokine-transduced tumors attract an inflammatory exudate in vivo that generally results in tumor destruction. The nature of the infiltrate (lymphocytic, mononuclear, granulocytic) cannot always be predicted from the known biological properties of each cytokine. Untransduced bystander tumor cells are usually also destroyed. Some, but not all, cytokine transductions result in the generation of systemic major histocompatibility complex-restricted, tumor immunity. It has been hypothesized that the local continuous production of cytokines by tumor cells provides an optimal microenvironment for antigen recognition and the generation of T-cell immunity.


CONCLUSIONS
These experimental observations hold promise for the clinical application of genetically engineered tumor vaccines.
Department of Surgery, UCLA Medical Center 90024-1782.
A R
AR
Miller
W H
WH
McBride
K
K
Hunt
J S
JS
Economou
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000627:therapeutic use; D007371:Interferon-gamma / Q000235:genetics / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics / Q000627:therapeutic use; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000627:therapeutic use
D016207:Cytokines; D016898:Interferon-alpha; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor