Gillisen et al. isolated tumor-specific antibodies from B cells of acute myeloid leukemia (AML) patients who had experienced durable remission following allogeneic hematopoietic stem cell transplantation. Several antibodies recognized the U5 snRNP200 complex, which is only expressed in the nucleus and cytoplasm of healthy cells, but is expressed on the surface of AML cells. These donor-derived antibodies induced non-apoptotic cell death of AML cells in vitro, and delayed tumor growth in a SCID mouse model of AML.
Most acute myeloid leukemia (AML) patients can only be cured when an allogeneic hematopoietic stem cell transplantation (HSCT) induces a graft versus leukemia immune response (GvL). While the role of T cells and NK cells in tumor immunology has been established, less is known about the contribution of B cells. From B cells of high-risk AML patients 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 non-hematopoietic 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 a FcR 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 anti-tumor responses.
Author Info: (1) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (2) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (3) Department of Hematology, Academ
Author Info: (1) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (2) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (3) Department of Hematology, Academic Medical Center, Amsterdam, Netherlands. (4) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (5) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (6) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (7) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (8) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (9) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (10) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (11) Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands. (12) Department of Medical Biochemistry, Academic Medical Center, Amsterdam, Netherlands. (13) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (14) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (15) AIMM Therapeutics, Academic Medical Center, Amsterdam, Netherlands. (16) Department of Hematology, Academic Medical Center, Amsterdam, Netherlands; m.d.hazenberg@amc.nl.
