Selective Elimination of Human Regulatory T Lymphocytes In Vitro With the Recombinant Immunotoxin LMB-2
Year: 2006
Type: article
Abstract: 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.
Source: Journal of Immunotherapy
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Award: G5920202408
OpenAlex ID: W2035847993