Ronald P. Taylor
Professor of Biochemistry & Molecular Genetics
Ph.D., Princeton University
Clearance of Pathogens

 

For more than 25 years our laboratory has engaged in the study and characterization of monoclonal antibodies and their use in several different clinical applications. We have a considerable level of experience in studying complement activation by, as well as effector cell-mediated killing of, tumor cells opsonized with monoclonal antibodies. Our laboratory discovered and has substantially characterized the shaving reaction, that is the loss of B cell-associated CD20 that occurs when chronic lymphocytic leukemia (CLL) patients are treated with the usual (high) doses of CD20 mAbs rituximab or ofatumuamb. We have demonstrated, in pilot clinical studies, that much lower doses of rituximab or ofatumuamb, given more frequently, may provide a more effective therapy. As a result, several trials for low-dose rituximab, at the Mayo Clinic (NCT00669318), at multiple centers in the US and in the United Kingdom are ongoing. Most recently we have demonstrated that the key limiting factor in many mAb-based immunotherapies of cancer is the exhaustion of effector functions, including complement and effector cell-mediated cytotoxicity. In view of our observations that compIement was substantially exhausted in CLL patients after rituximab infusion, we proposed that fresh frozen plasma (FFP) could be used as a complement source in conjunction with rituximab therapy for CLL. Two clinical trials investigating this approach are now ongoing, and several papers have appeared that have provided some evidence suggesting that FFP may indeed be beneficial when CLL patients are treated with rituximab.


Selected References

Taylor RP, Lindorfer MA, Zent CS. (2012) "Anti-CD20 antibody therapy for B-cell lymphomas." N Engl J Med. Aug 367:876-7; author reply 878. doi:10.1056/NEJMc1207378#SA1. [PubMed]

Beum PV, Peek EM, Lindorfer MA, Beurskens FJ, Engelberts PJ, Parren PW, van deWinkel JG, Taylor RP. (2011) "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." J Immunol. Sep 187:3438-47. doi: 10.4049/jimmunol.1101189. Epub 2011Aug 12. [PubMed]

Daubeuf S, Lindorfer MA, Taylor RP, Joly E, Hudrisier D. (2010) "The direction of plasma membrane exchange between lymphocytes and accessory cells by trogocytosis is influenced by the nature of the accessory cell." J Immunol. Feb 184:1897-908. doi: 10.4049/jimmunol.0901570. Epub 2010 Jan 20. [PubMed]

Beum PV, Lindorfer MA, Beurskens F, Stukenberg PT, Lokhorst HM, Pawluczkowycz AW,Parren PW, van de Winkel JG, Taylor RP. (2008) "Complement activation on B lymphocytes opsonized with rituximab or ofatumumab produces substantial changes in membrane structure preceding cell lysis." J Immunol. Jul 181:822-32. [PubMed]

Glennie MJ, French RR, Cragg MS, Taylor RP. (2007) "Mechanisms of killing by anti-CD20 monoclonal antibodies." Mol Immunol. 44(16):3823-37. [PubMed]

Taylor RP, Lindorfer MA. (2007) "Drug insight: the mechanism of action of rituximab in autoimmune disease--the immune complex decoy hypothesis." Nat Clin Pract Rheumatol. 3:86-95. [PubMed]

Williams ME, Densmore JJ, Pawluczkowycz AW, Beum PV, Kennedy AD, Lindorfer MA,Hamil SH, Eggleton JC, Taylor RP. (2006) "Thrice-weekly low-dose rituximab decreases CD20 loss via shaving and promotes enhanced targeting in chronic lymphocytic leukemia." J Immunol. Nov 177(10):7435-43. [PubMed]

Beum PV, Kennedy AD, Williams ME, Lindorfer MA, Taylor RP. (2006) "The shaving reaction: rituximab/CD20 complexes are removed from mantle cell lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes." J Immunol. Feb 176:2600-9. [PubMed]

Kennedy AD, Beum PV, Solga MD, DiLillo DJ, Lindorfer MA, Hess CE, Densmore JJ,Williams ME, Taylor RP. (2004) "Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia." J Immunol. Mar 172:3280-8. [PubMed]