Interleukin-21: updated review of Phase I and II clinical trials in metastatic renal cell carcinoma, metastatic melanoma and relapsed/refractory indolent non-Hodgkin's lymphoma.
BACKGROUND
In advanced renal cell cancer and malignant melanoma, the current FDA approved immune modulators, such as IL-2, are the only agents which provide a durable complete remission. These responses, however, occur in < 10% of treated patients and their applicability is limited to selected patients because of their toxicity. The identification of new immunotherapeutic agents with an improved response rate and toxicity profile would represent a significant advancement in the treatment of these malignancies.


METHODS
This is a comprehensive review of IL-21 including its pharmacology and current developmental status. A literature review was performed using all PubMed listed publications involving IL-21, including original research articles, reviews and abstracts. It also includes a review of current ongoing trials and information from the official product website.


RESULTS
Recombinant IL-21 (rIL-21) is a new immune modulator currently undergoing Phase I and II testing. It is a cytokine with a four helix structure that has structural and sequence homology to IL-2 and -15, but also possesses many unique biological properties. In this review, we evaluate the development, pharmacologic properties, safety profile and current clinical efficacy of rIL-21.


CONCLUSIONS
rIL-21 has an acceptable safety profile and encouraging single agent activity in early phase renal cell carcinoma and melanoma clinical trials.
Hashmi
Mehmood H
MH
Division of Hematology and Oncology, Department of Internal Medicine, University of Kansas Medical Center, 2330 Shawnee Mission Parkway, Mail Stop 5003, Westwood, KS 66202, USA. pvanveldhuizen@kumc.edu
Van Veldhuizen
Peter J
PJ
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D019317:Evidence-Based Medicine; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007378:Interleukins / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D051379:Mice; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D000098546:Interleukin-21
D000970:Antineoplastic Agents; D007378:Interleukins; D011994:Recombinant Proteins; D000098546:Interleukin-21