Pretargeted radioimmunotherapy for B-cell lymphomas.
Relapsed or treatment refractory B-cell lymphomas are currently incurable with conventional chemotherapy and radiation treatments. High-dose chemoradiotherapy and stem cell transplantation can cure some patients with relapsed or refractory lymphoma, but the majority of such patients die of progressive disease. We have investigated the potential utility of pretargeted radioimmunotherapy using monoclonal antibody-streptavidin, immunoconjugates, and fusion proteins in combination with N-acetylgalactosamine dendrimeric clearing agent and radiometal-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid biotin for treatment of lymphomas using mouse and primate models. We have targeted a variety of cell surface antigens, including CD20, CD22, CD45, and HLA-DR, using conventional and pretargeted radioimmunotherapy. These studies showed the marked superiority of pretargeted radioimmunotherapy for each of the antigenic targets in terms of superior biodistributions, more complete tumor regressions, and longer survival. We are optimistic that this novel approach will provide a meaningful prolongation of survival for patients with relapsed or refractory lymphomas.
Green
Damian J
DJ
Clinical Research Division, Fred Hutchinson Cancer Research Center, Department of Medicine, University of Washington, Seattle, Washington 98109, USA. dgreen@fhcrc.org
Pagel
John M
JM
Pantelias
Anastasia
A
Hedin
Nathan
N
Lin
Yukang
Y
Wilbur
D Scott
DS
Gopal
Ajay
A
Hamlin
Donald K
DK
Press
Oliver W
OW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D016393:Lymphoma, B-Cell / Q000532:radiotherapy*; D016499:Radioimmunotherapy
D000911:Antibodies, Monoclonal