期刊
PHARMACOLOGY & THERAPEUTICS
卷 111, 期 3, 页码 596-628出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2005.11.005
关键词
mda-7/IL-24; differentiation therapy of cancer; programmed cell death; antitumor bystander activity; radiosensitization; angiogenesis; cell signaling; Phase I clinical trial
资金
- NATIONAL CANCER INSTITUTE [R01CA088906, R01CA083821, R01CA098712, R01CA111569, R01CA108520, R01CA094084, R01CA035675, P01CA104177, R01CA097318, P01CA072955, R01CA093796, R01CA093738, R01CA100866, R01CA063753, R56CA094084] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK052825] Funding Source: NIH RePORTER
Differentiation therapy provides a unique and potentially effective, less toxic treatment paradigm for cancer. Moreover, combining differentiation therapy with molecular approaches presents an unparalleled opportunity to identify and clone genes mediating cancer growth control, differentiation, senescence, and programmed cell death (apoptosis). Subtraction hybridization applied to human melanoma cells induced to terminally differentiate by treatment with fibroblast interferon (IFN-beta) plus mezerein (MEZ) permitted cloning of melanoma differentiation associated (mda) genes. Founded on its novel properties, one particular mda gene, mda-7, now classified as a member of the interleukin (IL)-10 gene family (IL-24) because of conserved structure, chromosomal location, and cytokine-like properties has become the focus of attention of multiple laboratories. When administered by transfection or adenovirus-transduction into a spectrum of tumor cell types, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) induces apoptosis, whereas no toxicity is apparent in normal cells. mda-7/IL-24 displays potent bystander antitumor activity and also has the capacity to enhance radiation lethality, to induce immune-regulatory activities, and to inhibit tumor angiogenesis. Based on these remarkable attributes and effective antitumor therapy in animal models, this cytokine has taken the important step of entering the clinic. In a Phase I clinical trial, intratumoral injections of adenovirus-administered mda-7/IL-24 (Ad.mda-7) was safe, elicited tumor-regulatory and immune-activating processes, and provided clinically significant activity. This review highlights our current understanding of the diverse activities and properties of this novel cytokine, with potential to become a prominent gene therapy for cancer. (c) 2006 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据