Serum alters the uptake and biologic activity of CpG oligodeoxynucleotides in B cell chronic lymphocytic leukemia

Bernd Jahrsdörfer; Sue E Blackwell; James E Wooldridge; Christiana M Taylor; George J Weiner

doi:10.1089/oli.2005.15.51

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Journal article

Serum alters the uptake and biologic activity of CpG oligodeoxynucleotides in B cell chronic lymphocytic leukemia

Bernd Jahrsdörfer, Sue E Blackwell, James E Wooldridge, Christiana M Taylor and George J Weiner

Oligonucleotides, Vol.15(1), pp.51-59

2005

DOI: 10.1089/oli.2005.15.51

PMID: 15788900

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Abstract

Immunostimulatory CpG-containing oligodeoxynucleotides (CpG ODN) have a number of effects on B cells, including upregulation of immunogenic molecules, and, therefore, appear attractive as potential components of immunotherapy for B cell chronic lymphocytic leukemia (B-CLL). Previous in vitro studies investigating the effect of CpG ODN on B-CLL cells used serum-low conditions and did not account for the longer-half life of CpG ODN in vitro. The present study was designed to explore how the presence of serum and exposure time affect CpG ODN-mediated changes on B-CLL cells. The optimal concentration for CpG ODN-mediated effects in the presence of 100% serum or plasma was higher (10-20 microg/ml) than for serum-low conditions. Maximal CpG ODN-mediated effects required the presence of ODN for no longer than 3 hours. The inhibition of CpG ODN-mediated effects by serum correlated with lower uptake of ODN into B-CLL cells in the presence of serum. A threshold effect on biologic response was observed, with a given amount of ODN internalized, resulting in phenotypic changes. In conclusion, systemic short-term application of CpG ODN appears to be sufficient to induce phenotypic changes, but higher doses of CpG ODN than previously thought may be necessary because of inhibition of their uptake by serum.

Gene Transfer Techniques

Oligonucleotides - chemistry

Up-Regulation

Immunotherapy - methods

Humans

Immunophenotyping

Dose-Response Relationship, Drug

Phenotype

Flow Cytometry

Leukemia, B-Cell - genetics

Time Factors

CpG Islands - genetics

Culture Media, Serum-Free - pharmacology

Leukemia, Lymphoid - genetics

Details

Title: Subtitle: Serum alters the uptake and biologic activity of CpG oligodeoxynucleotides in B cell chronic lymphocytic leukemia
Creators: Bernd Jahrsdörfer - The Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA
Sue E Blackwell
James E Wooldridge
Christiana M Taylor
George J Weiner
Resource Type: Journal article
Publication Details: Oligonucleotides, Vol.15(1), pp.51-59
DOI: 10.1089/oli.2005.15.51
PMID: 15788900
ISSN: 1545-4576
eISSN: 1557-8526
Grant note: R01 CA77764 / NCI NIH HHS P50 CA97274-01 / NCI NIH HHS
Language: English
Date published: 2005
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9984094545902771

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