Immunostimulatory cytokines in somatic cells and gene therapy of cancer.
The use of immunostimulatory cytokines has become an increasingly promising approach in cancer immunotherapy. The major goal is the activation of tumour-specific T lymphocytes capable of rejecting tumour cells from patients with low tumour burden or to protect patients from a recurrence of the disease. Strategies that provide high levels of immunostimulatory cytokines locally at the site of antigen have demonstrated pre-clinical and occasional clinical efficacy. Animal models using poorly immunogenic tumours revealed that tumour cells genetically engineered to produce cytokines like IL-2, IL-4, IL-7, IL-12, IFNs, GM-CSF or TNF-alpha were found to be effective in eradicating disseminated tumours. Experimental data obtained from these different animal models are reviewed here to provide an overview of this rapidly evolving field. The data obtained so far from clinical trials involving cytokine gene-modified cells have provided important information regarding the feasibility, safety, immunological effects and occasional clinical responses.
Mackensen
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Department of Hematology/Oncology, Freiburg Medical University Center, Germany. mackensen@mm11.uk1.uni-freiburg.de
Lindemann
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Mertelsmann
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R
D000818:Animals; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology* / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology
D016207:Cytokines; D007376:Interleukin-2; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor