Salah-Eddine Bentebibel1, Adi Diab2. 1. Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. Sbentebibel@mdanderson.org. 2. Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. Adiab@mdanderson.org.
Abstract
PURPOSE OF REVIEW: The use of cytokines in harnessing the immune system to eradicate cancer has been an important treatment modality. However, the dose-limiting toxicities of these cytokines limited their usage in clinic. Here, we review the basic biology of cytokines involved in the treatment of melanoma and discuss their therapeutic applications. Moreover, we describe several innovative technological approaches that have been developed to improve the pharmacokinetics, safety, and efficacy of these cytokines. RECENT FINDINGS: The safety and the anti-tumor activity of newly engineered cytokines including PEGylated IL-2 (NKTR-214), PEGylated IL-10 (AM0010), and IL-15 super agonist (ALT-803) have been evaluated in clinical trials with encouraging clinical activity and acceptable safety profile, both as single agents and in combination with immuno-oncology agents. A greater understanding of the mechanisms of action and effective dosing of these newly engineered cytokine together with determination of optimum combination therapy regimens may yield greater clinical benefits in the future.
PURPOSE OF REVIEW: The use of cytokines in harnessing the immune system to eradicate cancer has been an important treatment modality. However, the dose-limiting toxicities of these cytokines limited their usage in clinic. Here, we review the basic biology of cytokines involved in the treatment of melanoma and discuss their therapeutic applications. Moreover, we describe several innovative technological approaches that have been developed to improve the pharmacokinetics, safety, and efficacy of these cytokines. RECENT FINDINGS: The safety and the anti-tumor activity of newly engineered cytokines including PEGylated IL-2 (NKTR-214), PEGylated IL-10 (AM0010), and IL-15 super agonist (ALT-803) have been evaluated in clinical trials with encouraging clinical activity and acceptable safety profile, both as single agents and in combination with immuno-oncology agents. A greater understanding of the mechanisms of action and effective dosing of these newly engineered cytokine together with determination of optimum combination therapy regimens may yield greater clinical benefits in the future.
Authors: E Jonasch; U N Kumar; G P Linette; F S Hodi; R J Soiffer; B F Ryan; A J Sober; M C Mihm; H Tsao; R G Langley; B A Cosimi; M A Gadd; K K Tanabe; W Souba; H A Haynes; R Barnhill; R Osteen; F G Haluska Journal: Cancer J Date: 2000 May-Jun Impact factor: 3.360