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.
Attia
Peter
P
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Powell
Daniel J
DJ
Maker
Ajay V
AV
Kreitman
Robert J
RJ
Pastan
Ira
I
Rosenberg
Steven A
SA
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