Eradication of B-CLL by autologous and allogeneic host nonreactive anti-third-party CTLs.

Blood
Fabian D ArdittiY Reisner

Abstract

Establishment of cell lines capable of killing leukemia cells, in the absence of alloreactivity against normal host cells, represents a most desirable goal in bone marrow transplantation (BMT) and cancer immunotherapy. By using a human --> mouse chimeric model, we demonstrate that allogeneic anti-third-party cytotoxic T lymphocytes (CTLs) depleted of alloreactivity are endowed with a potent anti-B-cell chronic lymphocytic leukemia (B-CLL) reactivity. Likewise, CTL preparations generated from autologous T cells of the same patients with B-CLL exhibited comparable leukemia eradication, suggesting that the reactivity of allogeneic anti-third-party CTLs is not mediated by residual antihost clones. This specificity was also exhibited in vitro, and annexin staining revealed that B-CLL killing is mediated by apoptosis. While the CTLs killing of third-party cells could be blocked by anti-CD3 antibody, the lysis of the B-CLL cells was not inhibited by this antibody, suggesting a T-cell receptor (TCR)-independent cytotoxicity. The role of cell contact leading to apoptosis of B-CLL cells is shown in transwell plates and by anti-lymphocyte function-associated antigen-1 (LFA-1)-blocking antibody. Up-regulation of CD54 and the subsequent apo...Continue Reading

References

May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·C WülfingM M Davis
Sep 25, 1998·Current Opinion in Hematology·T J Kipps
Aug 9, 2001·Reviews in Clinical and Experimental Hematology·F Caligaris-Cappio

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Citations

Jun 29, 2007·Nature Clinical Practice. Oncology·Ben SprangersAn D Billiau
Jan 20, 2009·International Immunopharmacology·Eran Ophir, Yair Reisner
Oct 13, 2007·Blood Cells, Molecules & Diseases·Maria De IoanniAntonio Tabilio
Jul 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Assaf LaskYair Reisner

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