Human cancer gene therapy with cytokine gene-modified cells.
Cytokines can impede tumour growth and activate innate and adaptive immune responses, leading to elimination of cancer cells. For many years, it was believed that systemic administration of recombinant cytokines might become a standard treatment of different cancer types. However, due to a high toxicity of therapeutic doses and a low efficacy, even in combination with chemotherapy, this strategy is generally not accepted. On the other hand, cancer gene therapy approaches utilising cells modified with cytokine genes seem to represent a novel promising approach. For the last decade, numerous Phase I and II clinical trials evaluating different therapies based on cytokine gene-modified cells have been carried out. In the early studies, several strategies have been shown to improve clinical outcomes and induce strong antitumour immune responses. Recently, a few prospective, randomised, Phase III clinical trials have been initiated in order to finally determine the efficacy of particular cancer immunogene therapy strategies. This article reviews the present status and perspectives of clinical trials of cancer immunotherapies utilising cytokine gene-modified cells.
University of Medical Sciences at GreatPoland Cancer Center, Department of Cancer Immunology, UL. Garbary 15, 61-866 Poznan, Poland.
Piotr J
PJ
Wysocki
A
A
Karczewska-Dzionk
M
M
Mackiewicz-Wysocka
A
A
Mackiewicz
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use; D017690:Cell Transplantation; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics* / Q000627:therapeutic use; D003673:Defective Viruses / Q000235:genetics; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007239:Infections / Q000503:physiopathology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000502:physiology / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000637:transplantation
D019496:Cancer Vaccines; D016207:Cytokines; D007378:Interleukins; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor