title: Recognition of antigen-specific B-cell receptors from chronic lymphocytic leukemia patients by synthetic antigen surrogates.
abstract: In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as synthetic antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used to identify other classes of antigen surrogates.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Mohosin
authors.initials: M
authors.lastname: Sarkar
authors.affiliation: The Karches Center for Chronic Lymphocytic Leukemia Research, Hofstra North Shore-LIJ School of Medicine, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Morimoto
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Haiyong
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Aquino
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA; Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Rader
authors.affiliation: The Karches Center for Chronic Lymphocytic Leukemia Research, Hofstra North Shore-LIJ School of Medicine, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chiorazzi
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, USA; Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA. Electronic address: kodadek@scripps.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kodadek
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D040761:Biomimetic Materials / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000951:Antigens, Neoplasm; D011947:Receptors, Antigen, B-Cell