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

Authors :
Gillissen, Marijn A.
Kedde, Martijn
Jong, Greta de
Moiset, Gemma
Yasuda, Etsuko
Levie, Sophie E.
Bakker, Arjen Q.
Claassen, Yvonne B.
Wagner, Koen
Böhne, Martino
Hensbergen, Paul J.
Speijer, Dave
van Helden, Pauline M.
Beaumont, Tim
Spits, Hergen
Hazenberg, Mette D.
Source :
Blood; January 2018, Vol. 131 Issue: 1 p131-143, 13p
Publication Year :
2018

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.

Details

Language :
English
ISSN :
00064971 and 15280020
Volume :
131
Issue :
1
Database :
Supplemental Index
Journal :
Blood
Publication Type :
Periodical
Accession number :
ejs44388506
Full Text :
https://doi.org/10.1182/blood-2017-02-768762