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Updated: Aug 10, 2026
Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance
Published on: July 22, 2011
Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2
Peter Attia1, Daniel J Powell, Ajay V Maker
1Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
CD4(+)CD25(+) T-regulatory cells (T(reg)) can inhibit the proliferation and cytokine secretion of CD4(+)CD25(-) helper T cells in mice and humans. In murine tumor models, the presence of these T(reg) cells can inhibit the antitumor effectiveness of T-cell transfer and active immunization approaches. We have thus initiated efforts to eliminate T(reg) cells selectively from human peripheral blood mononuclear cells (PBMCs) to potentially bolster antitumor responses. LMB-2 is a recombinant immunotoxin that is a fusion of a single-chain Fv fragment of the anti-Tac anti-CD25 monoclonal antibody to a truncated form of the bacterial Pseudomonas exotoxin A. In vitro incubation of human PBMCs with LMB-2 reduced the levels of CD4(+)CD25(+) and Foxp3-expressing cells without impairing the function of the remaining lymphocytes. The short in vivo half-life of LMB-2 makes it an attractive candidate for reducing human T(reg) cells in vivo before the administration of cancer vaccine or cell transfer immunotherapy approaches.
CD4(+)CD25(+) T-regulatory cells (T(reg)) can inhibit the proliferation and cytokine secretion of CD4(+)CD25(-) helper T cells in mice and humans. In murine tumor models, the presence of these T(reg) cells can inhibit the antitumor effectiveness of T-cell transfer and active immunization approaches. We have thus initiated efforts to eliminate T(reg) cells selectively from human peripheral blood mononuclear cells (PBMCs) to potentially bolster antitumor responses. LMB-2 is a recombinant immunotoxin that is a fusion of a single-chain Fv fragment of the anti-Tac anti-CD25 monoclonal antibody to a truncated form of the bacterial Pseudomonas exotoxin A. In vitro incubation of human PBMCs with LMB-2 reduced the levels of CD4(+)CD25(+) and Foxp3-expressing cells without impairing the function of the remaining lymphocytes. The short in vivo half-life of LMB-2 makes it an attractive candidate for reducing human T(reg) cells in vivo before the administration of cancer vaccine or cell transfer immunotherapy approaches.
