A Novel Potent Fas Agonist for Selective Depletion of Tumor Cells in Hematopoietic Transplants

Overview

Journal Blood Cancer J

Date 2012 Jul 26

PMID 22829095

Citations 2

Authors

A Nahimana

D Aubry

L Lagopoulos

P Greaney

A Attinger

S Demotz

K M Dawson

M Schapira

J Tschopp

M Dupuis

M A Duchosal

Affiliations

Soon will be listed here.

Abstract

There remains a clear need for effective tumor cell purging in autologous stem cell transplantation (ASCT) where residual malignant cells within the autograft contribute to disease relapse. Here we propose the use of a novel Fas agonist with potent pro-apoptotic activity, termed MegaFasL, as an effective ex-vivo purging agent. MegaFasL selectively kills hematological cancer cells from lymphomas and leukemias and prevents tumor development at concentrations that do not reduce the functional capacity of human hematopoietic stem/progenitor cells both in in vitro and in in vivo transplantation models. These findings highlight the potential use of MegaFasL as an ex-vivo purging agent in ASCT.

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References

Lee N, Cheong H, Kim S, Kim S, Kim C, Lee K . Ex vivo purging of leukemia cells using tumor-necrosis-factor-related apoptosis-inducing ligand in hematopoietic stem cell transplantation. Leukemia. 2003; 17(7):1375-83. DOI: 10.1038/sj.leu.2402960. View

Eppich H, Foxall R, Gaynor K, Dombkowski D, Miura N, Cheng T . Pulsed electric fields for selection of hematopoietic cells and depletion of tumor cell contaminants. Nat Biotechnol. 2000; 18(8):882-7. DOI: 10.1038/78504. View

Granena A, Castellsague X, Badell I, Ferra C, Ortega J, Brunet S . Autologous bone marrow transplantation for high risk acute lymphoblastic leukemia: clinical relevance of ex vivo bone marrow purging with monoclonal antibodies and complement. Bone Marrow Transplant. 1999; 24(6):621-7. DOI: 10.1038/sj.bmt.1701957. View

Dick J, Bhatia M, Gan O, Kapp U, Wang J . Assay of human stem cells by repopulation of NOD/SCID mice. Stem Cells. 1997; 15 Suppl 1:199-203; discussion 204-7. DOI: 10.1002/stem.5530150826. View

Mohr A, Zwacka R, Jarmy G, Buneker C, Schrezenmeier H, Dohner K . Caspase-8L expression protects CD34+ hematopoietic progenitor cells and leukemic cells from CD95-mediated apoptosis. Oncogene. 2005; 24(14):2421-9. DOI: 10.1038/sj.onc.1208432. View

Hildebrandt M, Serke S, Meyer O, Ebell W, Salama A . Immunomagnetic selection of CD34+ cells: factors influencing component purity and yield. Transfusion. 2000; 40(5):507-12. DOI: 10.1046/j.1537-2995.2000.40050507.x. View

Freedman A, Neuberg D, Mauch P, Soiffer R, Anderson K, Fisher D . Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. Blood. 1999; 94(10):3325-33. View

Berardi A, Meffre E, Pflumio F, Katz A, Vainchenker W, Schiff C . Individual CD34+CD38lowCD19-CD10- progenitor cells from human cord blood generate B lymphocytes and granulocytes. Blood. 1997; 89(10):3554-64. View

Duchosal M, Eming S, McCONAHEY P, Dixon F . Characterization of hu-PBL-SCID mice with high human immunoglobulin serum levels and graft-versus-host disease. Am J Pathol. 1992; 141(5):1097-113. PMC: 1886657. View

10.

Vormoor J, Lapidot T, Pflumio F, Risdon G, Patterson B, Broxmeyer H . Immature human cord blood progenitors engraft and proliferate to high levels in severe combined immunodeficient mice. Blood. 1994; 83(9):2489-97. View

11.

Mulroney C, Gluck S, Ho A . The use of photodynamic therapy in bone marrow purging. Semin Oncol. 1994; 21(6 Suppl 15):24-7. View

12.

Hogan C, Shpall E, McNulty O, McNiece I, Dick J, Shultz L . Engraftment and development of human CD34(+)-enriched cells from umbilical cord blood in NOD/LtSz-scid/scid mice. Blood. 1997; 90(1):85-96. View

13.

Lundell B, Vredenburgh J, Tyer C, DeSombre K, Smith A . Ex vivo expansion of bone marrow from breast cancer patients: reduction in tumor cell content through passive purging. Bone Marrow Transplant. 1998; 22(2):153-9. DOI: 10.1038/sj.bmt.1701314. View

14.

Deisseroth A, Zu Z, Claxton D, Hanania E, Fu S, Ellerson D . Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML. Blood. 1994; 83(10):3068-76. View

15.

Brenner M, Rill D, Moen R, Krance R, Mirro Jr J, Anderson W . Gene-marking to trace origin of relapse after autologous bone-marrow transplantation. Lancet. 1993; 341(8837):85-6. DOI: 10.1016/0140-6736(93)92560-g. View

16.

Craiu A, Saito Y, Limon A, Eppich H, Olson D, Rodrigues N . Flowing cells through pulsed electric fields efficiently purges stem cell preparations of contaminating myeloma cells while preserving stem cell function. Blood. 2004; 105(5):2235-8. DOI: 10.1182/blood-2003-12-4399. View

17.

Peter M, Budd R, Desbarats J, Hedrick S, Hueber A, Newell M . The CD95 receptor: apoptosis revisited. Cell. 2007; 129(3):447-50. DOI: 10.1016/j.cell.2007.04.031. View

18.

Anderson K, Andersen J, Soiffer R, Freedman A, Rabinowe S, Robertson M . Monoclonal antibody-purged bone marrow transplantation therapy for multiple myeloma. Blood. 1993; 82(8):2568-76. View

19.

Greaney P, Nahimana A, Lagopoulos L, Etter A, Aubry D, Attinger A . A Fas agonist induces high levels of apoptosis in haematological malignancies. Leuk Res. 2005; 30(4):415-26. DOI: 10.1016/j.leukres.2005.08.006. View

20.

Gertz M, Witzig T, Pineda A, Greipp P, Kyle R, Litzow M . Monoclonal plasma cells in the blood stem cell harvest from patients with multiple myeloma are associated with shortened relapse-free survival after transplantation. Bone Marrow Transplant. 1997; 19(4):337-42. DOI: 10.1038/sj.bmt.1700670. View