title: AFM analysis of the multiple types of molecular interactions involved in rituximab lymphoma therapy on patient tumor cells and NK cells.
abstract: Rituximab is a monoclonal antibody drug approved for the treatment of patients with lymphomas. Rituximab's main killing mechanism is antibody-dependent cellular cytotoxicity (ADCC). During ADCC, rituximab's fragment antigen binding (Fab) region binds to the CD20 antigen on the tumor cell and its fragment crystallizable (Fc) region binds to the Fc receptor (FcR) on the natural killer (NK) cells. In this study, two types of molecular interactions (CD20-rituximab, FcR-rituximab) involved in ADCC were measured simultaneously on cells prepared from biopsy specimens of lymphoma patients by utilizing atomic force microscopy (AFM) with functionalized tips carrying rituximab. NK cells were detected by specific NKp46 fluorescent labeling and tumor cells were detected by specific ROR1 fluorescent labeling. Based on the fluorescence recognition, the binding affinity and distribution of FcRs on NK cells, and CD20 on tumor cells, were quantitatively measured and mapped. The binding affinity and distribution of FcRs (on NK cells) and CD20 (on tumor cells) were associated with rituximab clinical efficacy. The experimental results provide a new approach to simultaneously quantify the multiple types of molecular interactions involved in rituximab ADCC mechanism on patient biopsy cells, which is of potential clinical significance to predict rituximab efficacy for personalized medicine.
authors.affiliation: State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071, China.
authors.forename: Xiubin
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071, China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China. Electronic address: lqliu@sia.cn.
authors.forename: Lianqing
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China; Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong, China. Electronic address: xin@egr.msu.edu.
authors.forename: Ning
authors.initials: N
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China.
authors.forename: Yuechao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology*; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008223:Lymphoma / Q000276:immunology*; D018625:Microscopy, Atomic Force; D011961:Receptors, Fc / Q000276:immunology*; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D011961:Receptors, Fc; D000069283:Rituximab
keywords: Antibody-dependent cellular cytotoxicity; Atomic force microscopy; CD20; Fc receptor; Lymphoma; Natural killer cell