Ronald P. Taylor
- BS, City College of New York, New York, NY
- PhD, Princeton University, Princeton, NJ
- Postdoc, University of Minnesota, Mpls., MN
- Professor, Biochemistry and Molecular Genetics
- Phone: 434-924-2664
- Email: firstname.lastname@example.org
Clearance of Pathogens: The role of complement in Immunotherapy: New approaches to vaccine generation
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.
- Baig N, Taylor R, Lindorfer M, Church A, LaPlant B, Pettinger A, Shanafelt T, Nowakowski G, Zent C. Induced resistance to ofatumumab-mediated cell clearance mechanisms, including complement-dependent cytotoxicity, in chronic lymphocytic leukemia. Journal of immunology (Baltimore, Md. : 1950). 2014;192(4): 1620-9. PMID: 24431228
- Da Roit F, Engelberts P, Taylor R, Breij E, Gritti G, Rambaldi A, Introna M, Parren P, Beurskens F, Golay J. Ibrutinib interferes with the cell-mediated anti-tumour activities of therapeutic CD20 antibodies: implications for combination therapy. Haematologica. 2014. PMID: 25344523
- Diebolder C, Beurskens F, de Jong R, Koning R, Strumane K, Lindorfer M, Voorhorst M, Ugurlar D, Rosati S, Heck A, van de Winkel J, Wilson I, Koster A, Taylor R, Saphire E, Burton D, Schuurman J, Gros P, Parren P. Complement is activated by IgG hexamers assembled at the cell surface. Science (New York, N.Y.). 2014;343(6176): 1260-3. PMID: 24626930
- Paixão-Cavalcante D, Torreira E, Lindorfer M, Rodriguez de Cordoba S, Morgan B, Taylor R, Llorca O, Harris C. A humanized antibody that regulates the alternative pathway convertase: potential for therapy of renal disease associated with nephritic factors. Journal of immunology (Baltimore, Md. : 1950). 2014;192(10): 4844-51. PMID: 24729617 | PMCID: PMC4066585
- Taylor R, Lindorfer M. Analyses of CD20 Monoclonal Antibody-Mediated Tumor Cell Killing Mechanisms: Rational Design of Dosing Strategies. Molecular pharmacology. 2014. PMID: 24944188 | PMCID: PMC4201137
- Zent C, Taylor R, Lindorfer M, Beum P, LaPlant B, Wu W, Call T, Bowen D, Conte M, Frederick L, Link B, Blackwell S, Veeramani S, Baig N, Viswanatha D, Weiner G, Witzig T. 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. American journal of hematology. 2014;89(7): 757-65. PMID: 24723493
- Mo C, Njuguna N, Beum P, Lindorfer M, Vire B, Lee E, Marti G, Wilson W, Taylor R, Wiestner A. Rapid clearance of rituximab may contribute to the continued high incidence of autoimmune hematologic complications of chemoimmunotherapy for chronic lymphocytic leukemia. Haematologica. 2013;98(8): 1259-63. PMID: 23716541 | PMCID: PMC3729907
- Pokrass M, Liu M, Lindorfer M, Taylor R. Activation of complement by monoclonal antibodies that target cell-associated β₂-microglobulin: implications for cancer immunotherapy. Molecular immunology. 2013;56(4): 549-60. PMID: 23911412
- Sharma R, Zhao H, Al-Saleem F, Ubaid A, Puligedda R, Segan A, Lindorfer M, Bermudez R, Elias M, Adekar S, Simpson L, Taylor R, Dessain S. Mechanisms of enhanced neutralization of botulinum neurotoxin by monoclonal antibodies conjugated to antibodies specific for the erythrocyte complement receptor. Molecular immunology. 2013;57(2): 247-54. PMID: 24184879 | PMCID: PMC3962830
- Taylor R, Lindorfer M. The role of complement in mAb-based therapies of cancer. Methods (San Diego, Calif.). 2013;65(1): 18-27. PMID: 23886909
- Baig N, Taylor R, Lindorfer M, Church A, Laplant B, Pavey E, Nowakowski G, Zent C. Complement dependent cytotoxicity in chronic lymphocytic leukemia: ofatumumab enhances alemtuzumab complement dependent cytotoxicity and reveals cells resistant to activated complement. Leukemia & lymphoma. 2012;53(11): 2218-27. PMID: 22475085
- Beurskens F, Lindorfer M, Farooqui M, Beum P, Engelberts P, Mackus W, Parren P, Wiestner A, Taylor R. Exhaustion of cytotoxic effector systems may limit monoclonal antibody-based immunotherapy in cancer patients. Journal of immunology (Baltimore, Md. : 1950). 2012;188(7): 3532-41. PMID: 22368276 | PMCID: PMC3311731
- Lindorfer M, Wiestner A, Zent C, Taylor R. Monoclonal antibody (mAb)-based cancer therapy: Is it time to reevaluate dosing strategies? Oncoimmunology. 2012;1(6): 959-961. PMID: 23162771 | PMCID: PMC3489759
- 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
- 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
- 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
- Taylor R, Lindorfer M. Immunotherapeutic mechanisms of anti-CD20 monoclonal antibodies. Current opinion in immunology. 2008;20(4): 444-9. PMID: 18585457 | PMCID: PMC2660201
- 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
- Taylor RP, Beum PV, Lindorfer MA. CD20 mAb-Mediated Complement Dependent Cytotoxicity of Tumor Cells is Enhanced by Blocking the Action of Factor I 598-616.
- Taylor RP, Koehl J, Lindorfer MA. Interactions between the Complement System and Fcγ Receptors .
- Taylor RP, Parren PWHI, Bakker J, Lindorfer MA. Ofatumumab: a next-generation human therapeutic CD20 antibody with potent complement-dependent cytotoxicity .