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Ipilimumab: controversies in its development, utility and autoimmune adverse events

  • Jeffrey Weber
Focussed Research Review

Abstract

A promising new class of anti-cancer drugs includes antibodies that mediate immune regulatory effects. It has become very clear over the last decade that different types of immune cells and different pathways serve to suppress anti-cancer immunity, particularly in the microenvironment of the tumor. The first examples of immune modulating antibodies are those directed against cytotoxic T lymphocyte antigen-4 (CTLA-4), a molecule present on activated T cells. Human antibodies that abrogate the function of CTLA-4 have been tested in the clinic and found to have clinical activity against melanoma. In this review, we discuss some of the controversies surrounding the potential clinical utility of one of those antibodies, ipilimumab, formerly MDX-010, from Medarex and Bristol Myers Squibb. The optimal dose and schedule of ipilimumab was derived in multiple clinical trials whose latest results are described below. Favorable survival in patients with stage IV melanoma were observed that appear to be associated with unique side effects of the drug called “immune-related adverse events”. The management of these side effects is described, and the unusual kinetics of anti-tumor response with ipilimumab as well as a newly proposed schema for assessing anti-tumor responses in patients receiving biologic compounds like ipilimumab, which may supercede RECIST or WHO criteria, are addressed.

Keywords

CTLA-4 Melanoma Antibody Ipilimumab T cell 

Notes

Acknowledgments

JW is a consultant for and receives research funding from Medarex and Bristol-Myers Squibb; JW is also a consultant for Pfizer.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.H. Lee Moffitt Cancer Center and Research Institute, Donald A. Adam Comprehensive Melanoma Research Center, Department of Oncologic SciencesUniversity of South FloridaTampaUSA

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