Immunotherapy using unconjugated CD19 monoclonal antibodies in animal models for B lymphocyte malignancies and autoimmune disease

doi:10.1073/pnas.0505539102

Immunotherapy using unconjugated CD19 monoclonal antibodies in animal models for B lymphocyte malignancies and autoimmune disease

Department of Immunology, Duke University Medical Center, Durham, NC 27710

Edited by Max D. Cooper, University of Alabama, Birmingham, AL (received for review June 30, 2005)

Abstract

Immunotherapy with unconjugated CD20 monoclonal antibodies has proven effective for treating non-Hodgkin's lymphoma and autoimmune disease. CD20 immunotherapy depletes mature B cells but does not effectively deplete pre-B or immature B cells, some B cell subpopulations, antibody-producing cells, or their malignant counterparts. Because CD19 is expressed earlier during B cell development, a therapeutic strategy for the treatment of early lymphoblastic leukemias/lymphomas was developed by using CD19-specific monoclonal antibodies in a transgenic mouse expressing human CD19. Pre-B cells and their malignant counterparts were depleted as well as antibody- and autoantibodyproducing cells. These results demonstrate clinical utility for the treatment of diverse B cell malignancies, autoimmune disease, and humoral transplant rejection.

Footnotes

↵ * To whom correspondence should be addressed. E-mail: thomas.tedder{at}duke.edu.
Author contributions: N.Y., Y.H., J.C.P., and T.F.T. designed research, performed research, analyzed data, and wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: hCD19TG mice, human CD19 transgenic mice; cMycTG, human c-Myc transgenic mice; TNP, 2,4,6-trinitrophenyl; DNP, 2,4-dinitrophenyl; KLH, keyhole limpet hemocyanin; ADCC, Ab-dependent cellular cytotoxicity; FcR, Fc receptor; FcγR, Fc receptor for IgG; FcRγ, common γ chain of the FcγR.