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Ronald P. Taylor

Ronald P. Taylor

Professor, Biochemistry and Molecular Genetics

Primary Location
PO Box 800733
1340 JPA Pinn Hall Room 6053A
Charlottesville, VA 22908
Primary Phone Number
Fax Number
434.924.5069

Bio & Overview

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 system. 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.

Academic Information

Department
Biochemistry and Molecular Genetics
Academic Title
Professor

Primary Education

  • BS, Chemistry, City College of New York, New York, NY, 1966
  • PhD, Physical Chemistry, Princeton University, Princeton, NJ, 1970
  • Postdoc, Physical Chemistry, University of Minnesota, Mpls., MN, 1973

Other Appointments

  • Professor, MII
  • Professor, BMBG
  • Professor, MOMD

Other Affiliations

  • Member, Immunology/Immunotherapy Program
  • Professor, BIMS

Research Interests

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

Research Disciplines

  • Biotechnology
  • Immunology
  • Translational Science

Research Opportunities

  • Biotechnology
  • Immunology

Selected Publications

Diebolder CA, Beurskens FJ, de Jong RN, Koning RI, Strumane K, Lindorfer MA, Voorhorst M, Ugurlar D, Rosati S, Heck AJ, van de Winkel JG, Wilson IA, Koster AJ, Taylor RP, Saphire EO, Burton DR, Schuurman J, Gros P, Parren PW, Complement is activated by IgG hexamers assembled at the cell surface., 2014; Science (New York, N.Y.). 343(6176) 1260-3. PMID: 24626930

Baig NA, Taylor RP, Lindorfer MA, Church AK, LaPlant BR, Pettinger AM, Shanafelt TD, Nowakowski GS, Zent CS, Induced resistance to ofatumumab-mediated cell clearance mechanisms, including complement-dependent cytotoxicity, in chronic lymphocytic leukemia., 2014; Journal of immunology (Baltimore, Md. : 1950). 192(4) 1620-9. PMID: 24431228

Taylor RP, Lindorfer MA, Analyses of CD20 Monoclonal Antibody-Mediated Tumor Cell Killing Mechanisms: Rational Design of Dosing Strategies., 2014; Molecular pharmacology. () . PMID: 24944188 | PMCID: PMC4201137

Paixão-Cavalcante D, Torreira E, Lindorfer MA, Rodriguez de Cordoba S, Morgan BP, Taylor RP, Llorca O, Harris CL, A humanized antibody that regulates the alternative pathway convertase: potential for therapy of renal disease associated with nephritic factors., 2014; Journal of immunology (Baltimore, Md. : 1950). 192(10) 4844-51. PMID: 24729617 | PMCID: PMC4066585

Zent CS, Taylor RP, Lindorfer MA, Beum PV, LaPlant B, Wu W, Call TG, Bowen DA, Conte MJ, Frederick LA, Link BK, Blackwell SE, Veeramani S, Baig NA, Viswanatha DS, Weiner GJ, Witzig TE, Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells., 2014; American journal of hematology. 89(7) 757-65. PMID: 24723493

Da Roit F, Engelberts PJ, Taylor RP, Breij EC, Gritti G, Rambaldi A, Introna M, Parren PW, Beurskens FJ, Golay J, Ibrutinib interferes with the cell-mediated anti-tumour activities of therapeutic CD20 antibodies: implications for combination therapy., 2014; Haematologica. () . PMID: 25344523

Taylor RP, Parren PWHI, Bakker J, Lindorfer MA, Ofatumumab: a next-generation human therapeutic CD20 antibody with potent complement-dependent cytotoxicity, 2014; . () . PMID:

Taylor RP, Koehl J, Lindorfer MA, Interactions between the Complement System and Fcγ Receptors, 2013; . () . PMID:

Mo CC, Njuguna N, Beum PV, Lindorfer MA, Vire B, Lee E, Marti G, Wilson WH, Taylor RP, Wiestner A, Rapid clearance of rituximab may contribute to the continued high incidence of autoimmune hematologic complications of chemoimmunotherapy for chronic lymphocytic leukemia., 2013; Haematologica. 98(8) 1259-63. PMID: 23716541 | PMCID: PMC3729907

Sharma R, Zhao H, Al-Saleem FH, Ubaid AS, Puligedda RD, Segan AT, Lindorfer MA, Bermudez R, Elias M, Adekar SP, Simpson LL, Taylor RP, Dessain SK, Mechanisms of enhanced neutralization of botulinum neurotoxin by monoclonal antibodies conjugated to antibodies specific for the erythrocyte complement receptor., 2013; Molecular immunology. 57(2) 247-54. PMID: 24184879 | PMCID: PMC3962830

Taylor RP, Lindorfer MA, The role of complement in mAb-based therapies of cancer., 2013; Methods (San Diego, Calif.). 65(1) 18-27. PMID: 23886909

Pokrass MJ, Liu MF, Lindorfer MA, Taylor RP, Activation of complement by monoclonal antibodies that target cell-associated β₂-microglobulin: implications for cancer immunotherapy., 2013; Molecular immunology. 56(4) 549-60. PMID: 23911412

Taylor RP, Beum PV, Lindorfer MA, CD20 mAb-Mediated Complement Dependent Cytotoxicity of Tumor Cells is Enhanced by Blocking the Action of Factor I, 2013; . () 598-616. PMID:

Baig NA, Taylor RP, Lindorfer MA, Church AK, Laplant BR, Pavey ES, Nowakowski GS, Zent CS, Complement dependent cytotoxicity in chronic lymphocytic leukemia: ofatumumab enhances alemtuzumab complement dependent cytotoxicity and reveals cells resistant to activated complement., 2012; Leukemia & lymphoma. 53(11) 2218-27. PMID: 22475085

Beurskens FJ, Lindorfer MA, Farooqui M, Beum PV, Engelberts P, Mackus WJ, Parren PW, Wiestner A, Taylor RP, Exhaustion of cytotoxic effector systems may limit monoclonal antibody-based immunotherapy in cancer patients., 2012; Journal of immunology (Baltimore, Md. : 1950). 188(7) 3532-41. PMID: 22368276 | PMCID: PMC3311731

Lindorfer MA, Wiestner A, Zent CS, Taylor RP, Monoclonal antibody (mAb)-based cancer therapy: Is it time to reevaluate dosing strategies?, 2012; Oncoimmunology. 1(6) 959-961. PMID: 23162771 | PMCID: PMC3489759

Daubeuf S, Lindorfer MA, Taylor RP, 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., 2010; Journal of immunology (Baltimore, Md. : 1950). 184(4) 1897-908. PMID: 20089699

Lindorfer MA, Pawluczkowycz AW, Peek EM, Hickman K, Taylor RP, Parker CJ, 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., 2010; Blood. 115(11) 2283-91. PMID: 20068220

Taylor RP, Lindorfer MA, Antigenic modulation and rituximab resistance., 2010; Seminars in hematology. 47(2) 124-32. PMID: 20350659 | PMCID: PMC2848181

Nyakoe NK, Taylor RP, Makumi JN, Waitumbi JN, Complement consumption in children with Plasmodium falciparum malaria., 2009; Malaria journal. 8() 7. PMID: 19134190 | PMCID: PMC2645421

Pawluczkowycz AW, Beurskens FJ, Beum PV, Lindorfer MA, van de Winkel JG, Parren PW, Taylor RP, 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., 2009; Journal of immunology (Baltimore, Md. : 1950). 183(1) 749-58. PMID: 19535640

Aue G, Lindorfer MA, Beum PV, Pawluczkowycz AW, Vire B, Hughes T, Taylor RP, Wiestner A, Fractionated subcutaneous rituximab is well-tolerated and preserves CD20 expression on tumor cells in patients with chronic lymphocytic leukemia., 2009; Haematologica. 95(2) 329-32. PMID: 19679883 | PMCID: PMC2817038

Taylor RP, Lindorfer MA, Immunotherapeutic mechanisms of anti-CD20 monoclonal antibodies., 2008; Current opinion in immunology. 20(4) 444-9. PMID: 18585457 | PMCID: PMC2660201

Taylor RP, Use of fresh frozen plasma to enhance the therapeutic action of rituximab., 2008; QJM : monthly journal of the Association of Physicians. 101(12) 991; author reply 991-2. PMID: 18829710

Whipple EC, Ditto AH, Shanahan RS, Gatesman JJ, Little SF, Taylor RP, Lindorfer MA, Low doses of antigen coupled to anti-CR2 mAbs induce rapid and enduring IgG immune responses in mice and in cynomolgus monkeys., 2006; Molecular immunology. 44(4) 377-88. PMID: 16631928

Beum PV, Kennedy AD, Williams ME, Lindorfer MA, Taylor RP, The shaving reaction: rituximab/CD20 complexes are removed from mantle cell lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes., 2006; Journal of immunology (Baltimore, Md. : 1950). 176(4) 2600-9. PMID: 16456022

Beum PV, Lindorfer MA, Hall BE, George TC, Frost K, Morrissey PJ, Taylor RP, Quantitative analysis of protein co-localization on B cells opsonized with rituximab and complement using the ImageStream multispectral imaging flow cytometer., 2006; Journal of immunological methods. 317(1) 90-9. PMID: 17067631