mda- 7/IL-24: A unique member of the IL-10 gene family promoting cancer-targeted toxicity

• Published in: Cytokine & growth factor reviews Vol. 21; no. 5; pp. 381 - 391
• Main Authors: Dash, Rupesh, Bhutia, Sujit K, Azab, Belal, Su, Zhao-zhong, Quinn, Bridget A, Kegelmen, Timothy P, Das, Swadesh K, Kim, Keetae, Lee, Seok-Geun, Park, Margaret A, Yacoub, Adly, Rahmani, Mohammed, Emdad, Luni, Dmitriev, Igor P, Wang, Xiang-Yang, Sarkar, Devanand, Grant, Steven, Dent, Paul, Curiel, David T, Fisher, Paul B
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2010
• Subjects: Advanced Basic Science; Amino Acid Sequence; Animals; Apoptosis; Autophagy; Bystander antitumor activity; Cancer terminator virus; Humans; Interleukin-10 - genetics; Interleukin-10 - pharmacology; Interleukins - genetics; Interleukins - pharmacology; mda-7/IL-24; Molecular Sequence Data; Neoplasms - drug therapy; Cancer terminator virus; mda-7/IL-24; Bystander antitumor activity; Autophagy; Apoptosis
• ISSN: 1359-6101; 1879-0305
• DOI: 10.1016/j.cytogfr.2010.08.004

Abstract Melanoma differentiation associated gene-7/interleukin-24 ( mda- 7/IL-24) is a unique member of the IL-10 gene family that displays nearly ubiquitous cancer-specific toxicity, with no harmful effects toward normal cells or tissues. mda- 7/IL-24 was cloned from human melanoma cells by differentiation induction subtraction hybridization (DISH) and promotes endoplasmic reticulum (ER) stress culminating in apoptosis or toxic autophagy in a broad-spectrum of human cancers, when assayed in cell culture, in vivo in human tumor xenograft mouse models and in a Phase I clinical trial in patients with advanced cancers. This therapeutically active cytokine also induces indirect antitumor activity through inhibition of angiogenesis, stimulation of an antitumor immune response, and sensitization of cancer cells to radiation-, chemotherapy- and antibody-induced killing.