Refractory colitis following anti-CTLA4 antibody therapy: analysis of mucosal FOXP3+ T cells.

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.

• Authors: James D Lord, Robert C Hackman, Amanda Moklebust, John A Thompson, Celestia S Higano, Deborah Chielens, Gideon Steinbach, George B McDonald
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 55 Issue 5 Pg. 1396-405 (May 2010) ISSN: 1573-2568 [Electronic] United States
• PMID: 19507029 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• FOXP3 protein, human
• Forkhead Transcription Factors
• Ipilimumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Biopsy
• Cause of Death
• Colitis (chemically induced, diagnosis, immunology)
• Female
• Forkhead Transcription Factors (immunology)
• Humans
• Ipilimumab
• Male
• Melanoma (drug therapy, immunology)
• Middle Aged
• Prostatic Neoplasms (drug therapy, immunology)
• Randomized Controlled Trials as Topic
• Treatment Outcome