Suppressive activity rather than frequency of FoxP3(+) regulatory T cells is essential for CA-125-specific T-cell activation after abagovomab treatment.

Abstract

The results of several clinical trials have clearly demonstrated the potential of the anti-idiotype (anti-Id) vaccine abagovomab to induce cancer antigen 125 (CA-125)-specific immunity in ovarian cancer patients. Because of the central role of regulatory T cells (Tregs) in tumor immunology, we analyzed the frequency and suppressive activity of CD25(+)FoxP3(+) Tregs in 16 patients treated with abagovomab. During vaccination, mean frequencies of peripheral Treg with a CD4(+)CD25(+)FoxP3(+) CD127(-) phenotype were enhanced but returned to baseline levels in the follow-up phase. Despite increasing Treg counts, the suppressive activity of Tregs was diminished in a subset of patients treated with abagovomab. Reduced Treg activity was associated with increasing polyclonal and CA-125-specific T-cell proliferation in these patients. Interestingly, CA-125-specific T-cell activation could not be further improved by Treg depletion in vitro, as CA-125 induced a suppressive CD4(+)CD25(+)FoxP3(+) CD127(-) T cell subset derived from the originally Treg-depleted T-cell fraction. These CA-125-induced Tregs (iTregs) efficiently blocked polyclonal and tumor-specific T-cell activation. Further elimination of iTregs resulted in detectable CA-125-specific T-cell responses in a subset of patients. Based on our results, the suppressive potential rather than the frequency of natural and CA-125-induced Tregs is an important issues to consider for refinement of current anti-Id vaccination.

• Authors: Silke Reinartz, Jacobus Pfisterer, Andreas du Bois, Christian Jackisch, Klaus H Baumann, Uwe Wagner
• Journal: Human immunology (Hum Immunol) Vol. 71 Issue 1 Pg. 36-44 (Jan 2010) ISSN: 1879-1166 [Electronic] United States
• PMID: 19782714 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• CA-125 Antigen
• FOXP3 protein, human
• Forkhead Transcription Factors
• abagovomab

Topics

• Antibodies, Monoclonal (immunology, therapeutic use)
• Antibodies, Monoclonal, Murine-Derived
• CA-125 Antigen (immunology)
• Cell Proliferation
• Cells, Cultured
• Female
• Forkhead Transcription Factors (immunology)
• Humans
• Lymphocyte Activation (immunology)
• Ovarian Neoplasms (drug therapy, immunology)
• T-Lymphocytes (cytology, immunology)
• T-Lymphocytes, Regulatory (immunology)