Advertisement

AML-specific cytotoxic antibodies in patients with durable graft-versus-leukemia responses

Marijn A. Gillissen, Martijn Kedde, Greta de Jong, Gemma Moiset, Etsuko Yasuda, Sophie E. Levie, Arjen Q. Bakker, Yvonne B. Claassen, Koen Wagner, Martino Böhne, Paul J. Hensbergen, Dave Speijer, Pauline M. van Helden, Tim Beaumont, Hergen Spits and Mette D. Hazenberg

Key Points

  • High-risk patients with AML with lasting GVL responses generate antibodies that kill leukemic blasts.

  • The target of these cytotoxic antibodies is the U5 snRNP200 complex, which is expressed on the membrane of AML blasts.

Publisher's Note: There is a Blood Commentary on this article in this issue.

Abstract

Most patients with acute myeloid leukemia (AML) can only be cured when allogeneic hematopoietic stem-cell transplantation induces a graft-versus-leukemia immune response (GVL). Although the role of T cells and natural killer cells in tumor immunology has been established, less is known about the contribution of B cells. From B cells of high-risk patients with AML with potent and lasting GVL responses, we isolated monoclonal antibodies directed against antigens expressed on the cell surface of AML cells but not on normal hematopoietic and nonhematopoietic cells. A number of these donor-derived antibodies recognized the U5 snRNP200 complex, a component of the spliceosome that in normal cells is found in the cell. In AML however, the U5 snRNP200 complex is exposed on the cell membrane of leukemic blasts. U5 snRNP200 complex–specific antibodies induced death of AML cells in an Fc receptor–dependent way in the absence of cytotoxic leukocytes or complement. In an AML mouse model, treatment with U5 snRNP200 complex–specific antibodies led to significant tumor growth inhibition. Thus, donor-derived U5 snRNP200 complex–recognizing AML-specific antibodies may contribute to antitumor responses.

  • Submitted February 14, 2017.
  • Accepted September 30, 2017.
View Full Text