A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy

Deirdre O'Mahony, John C. Morris, Cate Quinn, Wendy Gao, Wyndham H. Wilson, Barry Gause, Stefania Pittaluga, Sattva Neelapu, Margaret Brown, Thomas A. Fleisher, James L. Gulley, Jeffrey Schlom, Robert Nussenblatt, Paul Albert, Thomas A. Davis, Israel Lowy, Mike Petrus, Thomas A. Waldmann, John Edward Janik

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139 Scopus citations

Abstract

Purpose: Eleven patients with progressive advanced malignancy after administration of a cancer vaccine received a fully human anti-CTLA-4 monoclonal antibody (ipilimumab). The primary end point was to determine drug toxicity. Tumor response, tumor-specific CD8+ T-cell immune responses, and modulation of CD4+ CD25+ FoxP3+ regulatory T-cell (Treg) numbers were secondary end points. Experimental Design: Three patients with colon cancer, four with non - Hodgkin's lymphoma, and four with prostate cancer were treated. The first dose was given at 3 mg/kg and subsequent doses were administered monthly at 1.5 mg/kg for a total of four cycles. Results: Tumor regression was observed in two patients with lymphoma; one of which obtained a partial response of 14-month duration. Ipilimumab was well tolerated with predominantly grade 1/2 toxicities. One drug-related grade 3 toxicity was observed. One patient died within 30 days of treatment due to progressive colon cancer. No increase in vaccine-specific T-cell responses was observed after therapy. Tregs as detected by expression of CD4 +CD25+CD62L+ declined at early time points but rebounded to levels at or above baseline values at the time of the next infusion. Conclusions: Ipilimumab treatment depressed Treg numbers at early time points in the treatment cycle but was not accompanied by an increase in vaccine-specific CD8+ T-cell responses in these patients previously treated with a variety of investigational anticancer vaccines. A partial response was observed in one patient with follicular lymphoma. A phase I/II trial evaluating ipilimumab in patients with follicular lymphoma is currently ongoing.

Original languageEnglish (US)
Pages (from-to)958-964
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number3
DOIs
StatePublished - Feb 1 2007

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

O'Mahony, D., Morris, J. C., Quinn, C., Gao, W., Wilson, W. H., Gause, B., Pittaluga, S., Neelapu, S., Brown, M., Fleisher, T. A., Gulley, J. L., Schlom, J., Nussenblatt, R., Albert, P., Davis, T. A., Lowy, I., Petrus, M., Waldmann, T. A., & Janik, J. E. (2007). A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy. Clinical Cancer Research, 13(3), 958-964. https://doi.org/10.1158/1078-0432.CCR-06-1974