Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2.
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.
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Peter
P
Attia
Daniel J
DJ
Powell
Ajay V
AV
Maker
Robert J
RJ
Kreitman
Ira
I
Pastan
Steven A
SA
Rosenberg
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D019496:Cancer Vaccines; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D005098:Exotoxins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000008:administration & dosage* / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; C077707:B3(Fv)-PE38KDEL recombinant immunotoxin; D015704:CD4 Antigens; D019496:Cancer Vaccines; D005098:Exotoxins; D000922:Immunotoxins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins