Refractory Colitis Following Anti-CTLA4 Antibody Therapy: Analysis of Mucosal FOXP3(+) T Cells.

Lord, James D. and Hackman, Robert C. and Moklebust, Amanda and Thompson, John A. and Higano, Celestia S. and Chielens, Deborah and Steinbach, Gideon and McDonald, George B. (2010) Refractory Colitis Following Anti-CTLA4 Antibody Therapy: Analysis of Mucosal FOXP3(+) T Cells. Digestive diseases and sciences, 55 (5). pp. 1396-1405. ISSN 1573-2568

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Abstract

Ipilimumab is a humanized antibody to CTLA4 and is used to treat cancers refractory to conventional treatment. We treated 21 patients with refractory melanoma or prostate cancer with anti-CTLA4 antibody (ipilimumab), with subsequent development of significant colitis in nine cases. Two of these nine did not respond rapidly to high-dose (2 mg kg(-1) day(-1)) glucocorticoids or infliximab. They required additional immunosuppression, and one ultimately died of opportunistic infection, representing a more refractory course than has previously been described complicating ipilimumab therapy. Both patients had received radiation to the pelvis for prostate cancer less than 1 year prior to receiving ipilimumab. We performed immunohistochemical analysis of colon biopsies from ipilimumab recipients to determine if colitis correlates with depletion of intramucosal FOXP3(+) regulatory T cells (Tregs), which normally express CTLA4. However, we found no evidence of FOXP3(+) T cell depletion in any of the nine patients who developed colitis.

Item Type:	Article or Abstract
Additional Information:	This article is available to subscribers only via the URL above.
DOI:	10.1007/s10620-009-0839-8
PubMed ID:	19507029
NIHMSID:	NIHMS155479
PMCID:	PMC2904314
Grant Numbers:	R01 AI048779-05, T32 AI007411-15, P01 CA018029-240043
Keywords or MeSH Headings:	Adult Aged Aged, 80 and over Antibodies, Monoclonal/adverse effects* Antibodies, Monoclonal/therapeutic use Biopsy Cause of Death Colitis/chemically induced* Colitis/diagnosis Colitis/immunology Female Forkhead Transcription Factors/immunology Humans Male Melanoma/drug therapy* Melanoma/immunology Middle Aged Prostatic Neoplasms/drug therapy* Prostatic Neoplasms/immunology Randomized Controlled Trials as Topic Treatment Outcome
Depositing User:	Library Staff
Date Deposited:	27 Oct 2009 18:33
Last Modified:	14 Feb 2012 14:42
URI:	http://authors.fhcrc.org/id/eprint/344

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