Article citationsMore>>
Luqman, M., Klabunde, S., Lin, K., Georgakis, G.V., Cherukuri, A., Holash, J., Goldbeck, C., Xu, X., Kadel 3rd, E.E., Lee, S.H., Aukerman, S.L., Jallal, B., Aziz, N., Weng, W.K., Wierda, W., O’Brien, S. and Younes, A. (2008) The Antileukemia Activity of a Human Anti-CD40 Antagonist Antibody, HCD122, on Human Chronic Lymphocytic Leukemia Cells. Blood, 112, 711-720.
http://dx.doi.org/10.1182/blood-2007-04-084756
has been cited by the following article:
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TITLE:
Preclinical Evaluation of CD40-Directed Immunotherapy in B-Cell Lymphoma Using [18F]Fluorothymidine-PET
AUTHORS:
Nicolas Graf, Zhoulei Li, Ken Herrmann, Michaela Aichler, Jolanta Slawska, Axel Walch, Christian Peschel, Markus Schwaiger, Andreas K. Buck, Tobias Dechow, Ulrich Keller
KEYWORDS:
CD40 Antibody, FLT-PET, Lymphoma, Therapy Monitoring
JOURNAL NAME:
Advances in Molecular Imaging,
Vol.5 No.2,
April
9,
2015
ABSTRACT: Background: Inhibition of the lymphoma surface antigen CD40 by the
antagonistic CD40 antibody NVP-HCD122 (HCD122) demonstrates activity in various
lymphoma subtypes. In this preclinical in
vivo study we examined the suitability of positron emission tomography
(PET) using the thymidine analogue 3’-deoxy-3’-[18F]fluorothymidine
(FLT) for early response assessment upon HCD122 treatment in diffuse large B
cell lymphoma (DLBCL). Methods: Immunodeficient mice bearing human DLBCL
xenografts (SU-DHL-4) received weekly intraperitoneal injections of HCD122.
Tumor growth was followed up until Day 14. Molecular imaging with FLT-PET was
performed before (Day 0) and after start of therapy (Day 2 and Day 7). On Day 14
lymphoma xenografts were explanted for immunohistochemical analysis to correlate
PET findings with CD40 surface expression on tumor tissue. Results: Treatment
with HCD122 significantly delayed tumor growth resulting in a tumor growth
inhibition of 45% on Day 14. Significant reduction of tumor-to-background ratio
(TBR) of FLT-PET was seen in treated animals on Day 7 and preceded change of
tumor volume, thus predicting therapy response to HCD122. Immunohistochemical
analysis of xenografts revealed significantly higher CD40 expression on treated
than on untreated tissue. Moreover, we found a significant correlation between
CD40 expression and FLT-PET response for xenograft tumor treated with HCD122. Conclusions:
Treatment of DLBCL with the antagonistic CD40 antibody HCD122 can be monitored
with FLT-PET as early as seven days after commencement of therapy and seems to
increase CD40 expression on tumor tissue.
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