title: CD229 is expressed on the surface of plasma cells carrying an aberrant phenotype and chemotherapy-resistant precursor cells in multiple myeloma.
abstract: Multiple Myeloma (MM) is a plasma cell (PC) malignancy, which despite significant therapeutic advances, is still considered incurable. This is due to the persistence of chemotherapy-resistant minimal residual disease in the patients' bone marrow (BM) after an effective induction therapy. Immunotherapies targeting surface molecules expressed on the bulk of tumor cells and the chemotherapy-resistant, myeloma-propagating cells could play a central role in this clinical setting. We recently described surface molecule CD229 as a potential therapeutic target for MM. In our current study we assessed the expression of CD229 on different PC subtypes and on cells with a myeloma-propagating phenotype in a total of 77 patients with PC dyscrasias independently at 2 different cancer centers. We found that CD229 was strongly and homogeneously overexpressed on the PC of patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, MM, and PC leukemia. CD229 was particularly overexpressed on those PC showing an abnormal phenotype such as expression of CD56. Most importantly, CD229 was also highly expressed on those cells in the patients' BM displaying the phenotype of chemotherapy-resistant and myeloma-propagating cells. In conclusion, our combined findings suggest that immunotherapies targeting CD229 will not only be effective for the bulk of tumor cells but will also help to eradicate chemotherapy-resistant cells remaining in the patients' BM after induction treatment. Hopefully, the design of CD229-specific monoclonal antibodies or chimeric antigen receptor-transduced T cells will help to achieve prolonged remissions or even cures in MM patients.
authors.affiliation: a Hematology and Hematologic Malignancies; University of Utah; Huntsman Cancer Institute ; Salt Lake City , UT , USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Yousef
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kovacsovics-Bankowski
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Salama
authors.forename: Neelam
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Mary
authors.initials: M
authors.lastname: Steinbach
authors.forename: Amanda
authors.initials: A
authors.lastname: Langemo
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovacsovics
authors.forename: James
authors.initials: J
authors.lastname: Marvin
authors.forename: Mascha
authors.initials: M
authors.lastname: Binder
authors.forename: Jens
authors.initials: J
authors.lastname: Panse
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Tim
authors.initials: T
authors.lastname: Luetkens
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology; D010641:Phenotype; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D015703:Antigens, CD; D019002:CD56 Antigen; C430423:LY9 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family
keywords: CD229; SLAM family of receptors; immunotherapy; multiple myeloma; plasma cell dyscrasias; tumor immunology