title: Depletion of Alloreactive T-Cells by Anti-CD137-Saporin Immunotoxin.
abstract: Depletion of alloreactive T-lymphocytes from allogeneic bone marrow transplants may prevent graft-versus-host disease (GVHD) without impairing donor cell engraftment, immunity, and the graft-versus-leukemia (GVL) effect. Alloreactive T-cells may be identified by their expression, upon activation, of CD137, a costimulatory receptor and putative surrogate marker for antigen-specific effector T-cells. In this context, we tested the use of anti-CD137-saporin immunotoxin to selectively deplete mouse and human alloreactive T-cells. Anti-CD137 antibodies were internalized by cells within 4 h of binding to the cell surface CD137, and anti-CD137-saporin immunotoxin effectively killed polyclonally activated T-cells or antigen-stimulated T-cells. Transfer of donor T-cells after allodepletion with anti-CD137-saporin immunotoxin failed to induce any evident expression of GVHD; however, a significant GVL effect was observed. Targeting of CD137 with an immunotoxin was also effective in killing polyclonally activated or alloreactive human T-cells. Our results indicate that anti-CD137-saporin immunotoxin may be used to deplete alloreactive T-cells prior to bone marrow transplantation and thereby prevent GVHD and the relapse of leukemia.
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Sang C
authors.initials: SC
authors.lastname: Lee
authors.forename: Kwang W
authors.initials: KW
authors.lastname: Seo
authors.forename: Hye J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sang W
authors.initials: SW
authors.lastname: Kang
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Choi
authors.forename: Ansuk
authors.initials: A
authors.lastname: Kim
authors.forename: Byoung S
authors.initials: BS
authors.lastname: Kwon
authors.forename: Hong R
authors.initials: HR
authors.lastname: Cho
authors.forename: Byungsuk
authors.initials: B
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity*; D007938:Leukemia / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion / Q000379:methods*; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1 / Q000633:toxicity*; D000076985:Saporins; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014184:Transplantation, Homologous; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D000076985:Saporins