Gillissen et al. searched the B cell repertoire of a patient who had experienced a durable graft-versus-AML response following HSCT treatment and identified an antibody, AT1413, which specifically recognized a unique sialylated epitope of CD43 overexpressed in AML, and demonstrated presence of this epitope on all 61 patient-derived leukemic blasts (representing all WHO classifications of AML) that were tested. AT1413 showed antitumor cytotoxicity in vitro and in vivo while sparing non-malignant cells, supporting consideration for clinical evaluation.
Immunotherapy has proven beneficial in many hematologic and nonhematologic malignancies, but immunotherapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is hampered by the lack of tumor-specific targets. We took advantage of the tumor-immunotherapeutic effect of allogeneic hematopoietic stem cell transplantation and searched the B-cell repertoire of a patient with a lasting and potent graft-versus-AML response for the presence of AML-specific antibodies. We identified an antibody, AT1413, that was of donor origin and that specifically recognizes a novel sialylated epitope on CD43 (CD43s). Strikingly, CD43s is expressed on all World Health Organization 2008 types of AML and MDS. AT1413 induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of AML cells in vitro. Of note, AT1413 was highly efficacious against AML cells in a humanized mouse model without affecting nonmalignant human myeloid cells, suggesting AT1413 has potential as a therapeutic antibody.
Author Info: (1) AIMM Therapeutics, Amsterdam, The Netherlands. Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands. (2) AIMM Therapeutics, Amsterdam, The Netherlands.
Author Info: (1) AIMM Therapeutics, Amsterdam, The Netherlands. Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands. (2) AIMM Therapeutics, Amsterdam, The Netherlands. Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands. (3) AIMM Therapeutics, Amsterdam, The Netherlands. (4) AIMM Therapeutics, Amsterdam, The Netherlands. (5) AIMM Therapeutics, Amsterdam, The Netherlands. (6) AIMM Therapeutics, Amsterdam, The Netherlands. (7) Center for Proteomics and Metabolomics, University Medical Center, Leiden, The Netherlands; and. (8) AIMM Therapeutics, Amsterdam, The Netherlands. (9) AIMM Therapeutics, Amsterdam, The Netherlands. (10) AIMM Therapeutics, Amsterdam, The Netherlands. (11) AIMM Therapeutics, Amsterdam, The Netherlands. (12) AIMM Therapeutics, Amsterdam, The Netherlands. Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands. (13) Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands. Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
