scholarly journals Real Time Analysis of Binding between Rituximab (Anti-CD20 Antibody) and B Lymphoma Cells

2013 ◽  
Vol 85 (18) ◽  
pp. 8543-8551 ◽  
Author(s):  
Liang Tan ◽  
Peiling Lin ◽  
Mohammad M. Chisti ◽  
Abdul Rehman ◽  
Xiangqun Zeng
2008 ◽  
Vol 15 (4) ◽  
pp. 463-471 ◽  
Author(s):  
Daisuke Danno ◽  
Masatoshi Kanno ◽  
Shinichi Fujimoto ◽  
Loreto B. Feril ◽  
Takashi Kondo ◽  
...  

2001 ◽  
Vol 46 (14) ◽  
pp. 1182-1186 ◽  
Author(s):  
Zengzu Lai ◽  
Dongsheng Xiong ◽  
Dongmei Fan ◽  
Yuanfu Xu ◽  
Hanzhi Liu ◽  
...  

2018 ◽  
Vol 46 (sup2) ◽  
pp. 1063-1073 ◽  
Author(s):  
Xiaolong Tang ◽  
Chunmei Xie ◽  
Zhenyou Jiang ◽  
Amin Li ◽  
Shiyu Cai ◽  
...  

Author(s):  
Dieke J. van Rees ◽  
Maximilian Brinkhaus ◽  
Bart Klein ◽  
Paul Verkuijlen ◽  
Anton T.J. Tool ◽  
...  

Anti-CD20 antibodies, like rituximab, are broadly used to treat B cell malignancies. These antibodies can induce various effector functions, including immune cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can induce ADCC towards solid cancer cells by trogoptosis, a cytotoxic mechanism known to be dependent on trogocytosis. However, neutrophils appear incapable of killing rituximab-opsonized B lymphoma cells. Nevertheless, neutrophils do trogocytose rituximab-opsonized B lymphoma cells, yet this only reduces CD20 surface expression, and is thought to render tumor cells therapeutically resistant to further rituximab-dependent destruction. Here, we demonstrate that resistance of B lymphoma cells towards neutrophil killing can be overcome by a combination of CD47-SIRPα checkpoint blockade and sodium stibogluconate (SSG), an anti-leishmanial drug and documented inhibitor of the tyrosine phosphatase SHP-1. SSG enhanced neutrophil-mediated ADCC of solid tumor cells, but enabled B lymphoma cell trogoptotic killing, by turning trogocytosis from a resistance-contributing mechanism into a cytotoxic anti-cancer one. The killing in the presence of SSG required both antibody opsonization of the target cells, as well as disruption of CD47-SIRPα interactions. These results provide a more detailed understanding of the role of neutrophil trogocytosis in antibody-mediated destruction of B cells and clues on how to further optimize antibody therapy of B cell malignancies.


Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1392-1398 ◽  
Author(s):  
Maria-Ana Ghetie ◽  
Helen Bright ◽  
Ellen S. Vitetta

In 1997, a chimeric anti-CD20 monoclonal antibody (mAb) (Rituxan) was approved for the treatment of low-grade/follicular B-cell lymphoma. Rituxan has a long half-life and low immunogenicity, and it mediates effector function. Rituxan induces apoptosis in some tumor cell lines in vitro. Previous studies with mAbs that react with neoplastic B cells have demonstrated that homodimers of immunoglobulin G ([IgG]2) often inhibit cell growth more effectively than their monomeric (IgG)1counterparts. In this study, the ability of IgG or F(ab′)2 homodimers vs monomers of Rituxan were compared for their ability to inhibit the growth of several different B-lymphoma cell lines in vitro. It was found that homodimers of Rituxan had superior antigrowth activity in vitro and that F(ab′)2 homodimers were the most active. Homodimers, but not monomers, of Rituxan induced both apoptosis and necrosis of several B-cell lymphoma lines in vitro; the inhibition of cell growth was not dependent upon the presence of Fc receptors or upon 10-fold or greater differences in the density of CD20 on the target cells. Rituxan homodimers, compared with monomers, also rendered drug-resistant CD20+ B-lymphoma cells more sensitive to chemotherapeutic agents and synergized with an anti-CD22 immunotoxin in vitro.


Author(s):  
R.P. Goehner ◽  
W.T. Hatfield ◽  
Prakash Rao

Computer programs are now available in various laboratories for the indexing and simulation of transmission electron diffraction patterns. Although these programs address themselves to the solution of various aspects of the indexing and simulation process, the ultimate goal is to perform real time diffraction pattern analysis directly off of the imaging screen of the transmission electron microscope. The program to be described in this paper represents one step prior to real time analysis. It involves the combination of two programs, described in an earlier paper(l), into a single program for use on an interactive basis with a minicomputer. In our case, the minicomputer is an INTERDATA 70 equipped with a Tektronix 4010-1 graphical display terminal and hard copy unit.A simplified flow diagram of the combined program, written in Fortran IV, is shown in Figure 1. It consists of two programs INDEX and TEDP which index and simulate electron diffraction patterns respectively. The user has the option of choosing either the indexing or simulating aspects of the combined program.


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