Ronald P. Taylor

Education

  • BS, City College of New York, New York, NY
  • PhD, Princeton University, Princeton, NJ
  • Postdoc, University of Minnesota, Mpls., MN

Primary Appointment

  • Professor, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

Clearance of Pathogens: The role of complement in Immunotherapy: New approaches to vaccine generation

Research Description

The long-term goal of our research is to provide an experimental foundation for the general treatment of infectious diseases through use of heteropolymer (HP)-sensitized human erythrocytes (RBCs). We have prepared bi-specific cross-linked monoclonal antibodies (HPs) with specificity for both selected targeted pathogens and the human erythrocyte C3b complement receptor (CR1). These HPs facilitate rapid and quantitative in vitro binding of targeted pathogens to CR1 on human and other primate RBCs. The use of HPs allows us to bypass the complement opsonization requirement for binding of immune complex substrates to CR1. Virtually any potential pathogen can be selectively bound to RBCs by this procedure. The HPs facilitate in vivo binding of innocuous prototype pathogens to primate RBCs, and these RBC-bound substrates and HP are rapidly cleared from the circulation without any lysis or sequestration of the RBCs. This result is a manifestation of one of the body's natural defenses, the RBC-based immune complex clearance mechanism. This mechanism allows for the safe and rapid neutralization and clearance of complement-opsonized pathogens bound to CR1 on human and non-human primate RBCs. We are now investigating whether virulent pathogens will be bound in vivo to RBCs via appropriately constructed HPs, and then rapidly and safely cleared from the circulation. Selected particulate pathogens include several bacteria and viruses.

We are also developing general approaches for the treatment of cancer based on the interaction of cancer cells with the complement sysstem. In the presence of serum and normal human IgM and/or specific monoclonal antibodies, large amounts of the complement activation product, C3bi, covalently bind to the cancer cells. We are using monoclonal antibodies specific for cell-associated C3bi to facilitate tumor cell targeting and killing.

Selected Publications

  • Beum P, Lindorfer M, Peek E, Stukenberg P, de Weers M, Beurskens F, Parren P, van de Winkel J, Taylor R. Penetration of antibody-opsonized cells by the membrane attack complex of complement promotes Ca(2+) influx and induces streamers. European journal of immunology. 2011;41(8): 2436-46. PMID: 21674476
  • Beum P, Peek E, Lindorfer M, Beurskens F, Engelberts P, Parren P, van de Winkel J, Taylor R. Loss of CD20 and bound CD20 antibody from opsonized B cells occurs more rapidly because of trogocytosis mediated by Fc receptor-expressing effector cells than direct internalization by the B cells. Journal of immunology (Baltimore, Md. : 1950). 2011;187(6): 3438-47. PMID: 21841127
  • Daubeuf S, Lindorfer M, Taylor R, Joly E, Hudrisier D. The direction of plasma membrane exchange between lymphocytes and accessory cells by trogocytosis is influenced by the nature of the accessory cell. Journal of immunology (Baltimore, Md. : 1950). 2010;184(4): 1897-908. PMID: 20089699
  • Lindorfer M, Pawluczkowycz A, Peek E, Hickman K, Taylor R, Parker C. A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement. Blood. 2010;115(11): 2283-91. PMID: 20068220
  • Taylor R, Lindorfer M. Antigenic modulation and rituximab resistance. Seminars in hematology. 2010;47(2): 124-32. PMID: 20350659 | PMCID: PMC2848181
  • Wada H, Yates D, Evers D, Taylor R, Hopkins W. Tissue mercury concentrations and adrenocortical responses of female big brown bats (Eptesicus fuscus) near a contaminated river. Ecotoxicology (London, England). 2010;19(7): 1277-84. PMID: 20596767
  • Aue G, Lindorfer M, Beum P, Pawluczkowycz A, Vire B, Hughes T, Taylor R, Wiestner A. Fractionated subcutaneous rituximab is well-tolerated and preserves CD20 expression on tumor cells in patients with chronic lymphocytic leukemia. Haematologica. 2009;95(2): 329-32. PMID: 19679883 | PMCID: PMC2817038
  • Nyakoe N, Taylor R, Makumi J, Waitumbi J. Complement consumption in children with Plasmodium falciparum malaria. Malaria journal. 2009;8 7. PMID: 19134190 | PMCID: PMC2645421
  • Pawluczkowycz A, Beurskens F, Beum P, Lindorfer M, van de Winkel J, Parren P, Taylor R. Binding of submaximal C1q promotes complement-dependent cytotoxicity (CDC) of B cells opsonized with anti-CD20 mAbs ofatumumab (OFA) or rituximab (RTX): considerably higher levels of CDC are induced by OFA than by RTX. Journal of immunology (Baltimore, Md. : 1950). 2009;183(1): 749-58. PMID: 19535640
  • Taylor R, Lindorfer M. Impact of low-dose rituximab on splenic B cells: evidence for the shaving reaction. Transplant international : official journal of the European Society for Organ Transplantation. 2009;23(1): 116-7. PMID: 19624496
  • Use of fresh frozen plasma to enhance the therapeutic action of rituximab. QJM : monthly journal of the Association of Physicians. 2008;101(12): 991; author reply 991-2. PMID: 18829710
  • Beum P, Lindorfer M, Taylor R. Within peripheral blood mononuclear cells, antibody-dependent cellular cytotoxicity of rituximab-opsonized Daudi cells is promoted by NK cells and inhibited by monocytes due to shaving. Journal of immunology (Baltimore, Md. : 1950). 2008;181(4): 2916-24. PMID: 18684983
  • Beum P, Mack D, Pawluczkowycz A, Lindorfer M, Taylor R. Binding of rituximab, trastuzumab, cetuximab, or mAb T101 to cancer cells promotes trogocytosis mediated by THP-1 cells and monocytes. Journal of immunology (Baltimore, Md. : 1950). 2008;181(11): 8120-32. PMID: 19018005
  • D'Arena G, Taylor R, Cascavilla N, Lindorfer M. Monoclonal antibodies: new therapeutic agents for autoimmune hemolytic anemia? Endocrine, metabolic & immune disorders drug targets. 2008;8(1): 62-8. PMID: 18393924
  • Taylor R, Lindorfer M. Immunotherapeutic mechanisms of anti-CD20 monoclonal antibodies. Current opinion in immunology. 2008;20(4): 444-9. PMID: 18585457 | PMCID: PMC2660201
  • Of mice and mechanisms: identifying the role of complement in monoclonal antibody-based immunotherapy. Haematologica. 2006;91(2): 146a. PMID: 16461291
  • Beum P, Kennedy A, Williams M, Lindorfer M, Taylor R. The shaving reaction: rituximab/CD20 complexes are removed from mantle cell lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes. Journal of immunology (Baltimore, Md. : 1950). 2006;176(4): 2600-9. PMID: 16456022
  • Beum P, Lindorfer M, Hall B, George T, Frost K, Morrissey P, Taylor R. Quantitative analysis of protein co-localization on B cells opsonized with rituximab and complement using the ImageStream multispectral imaging flow cytometer. Journal of immunological methods. 2006;317(1): 90-9. PMID: 17067631
  • Whipple E, Ditto A, Shanahan R, Gatesman J, Little S, Taylor R, Lindorfer M. Low doses of antigen coupled to anti-CR2 mAbs induce rapid and enduring IgG immune responses in mice and in cynomolgus monkeys. Molecular immunology. 2006;44(4): 377-88. PMID: 16631928
  • Williams M, Densmore J, Pawluczkowycz A, Beum P, Kennedy A, Lindorfer M, Hamil S, Eggleton J, Taylor R. Thrice-weekly low-dose rituximab decreases CD20 loss via shaving and promotes enhanced targeting in chronic lymphocytic leukemia. Journal of immunology (Baltimore, Md. : 1950). 2006;177(10): 7435-43. PMID: 17082663