title: Activated marrow-infiltrating lymphocytes effectively target plasma cells and their clonogenic precursors.
abstract: A major limitation of adoptive immunotherapy is the availability of T cells specific for both terminally differentiated tumor cells and their clonogenic precursors. We show here that marrow-infiltrating lymphocytes (MILs) recognize myeloma cells after activation with anti-CD3/CD28 beads with higher frequency than activated peripheral blood lymphocytes from the same patients. Furthermore, activated MILs target both the terminally differentiated CD138+ plasma cells and the myeloma precursor as shown by profound inhibition in a tumor clonogenic assay. The presence of antigen in the marrow microenvironment seems to be important for the maintenance of tumor specificity. Taken together, these results highlight the intrinsic tumor specificity of MILs and describe a novel approach for the generation of tumor-specific T-cell populations suitable for adoptive immunotherapy of multiple myeloma.
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, Baltimore, Maryland 21231, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Noonan
authors.forename: William
authors.initials: W
authors.lastname: Matsui
authors.forename: Paolo
authors.initials: P
authors.lastname: Serafini
authors.forename: Rebecca
authors.initials: R
authors.lastname: Carbley
authors.forename: Gladys
authors.initials: G
authors.lastname: Tan
authors.forename: Jahan
authors.initials: J
authors.lastname: Khalili
authors.forename: Mark
authors.initials: M
authors.lastname: Bonyhadi
authors.forename: Hyam
authors.initials: H
authors.lastname: Levitsky
authors.forename: Katie
authors.initials: K
authors.lastname: Whartenby
authors.forename: Ivan
authors.initials: I
authors.lastname: Borrello
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D010950:Plasma Cells / Q000276:immunology*; D011509:Proteoglycans / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018106:CD28 Antigens; D017252:CD3 Complex; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011948:Receptors, Antigen, T-Cell; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D020169:Caspases