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PMID: 9486984 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells.

The Journal of clinical investigation ·Vol. 101 ·No. 5 ·1998-03-01 ·Pages 1133-41

Kato K, Cantwell MJ, Sharma S, Kipps TJ

Abstract

CD40-CD40-ligand (CD154) interactions play a critical role in immune activation. Using replication defective adenovirus encoding mouse CD154 (Ad-CD154), we modified human chronic lymphocytic leukemia B cells to express a functional ligand for CD40. This not only induces expression of immune accessory molecules on the infected cell, but also allows it to trans-activate noninfected bystander leukemia B cells. Also, factors that impair the antigen-presenting capacity of leukemia B cells are downmodulated. Ad-CD154- infected leukemia cells are highly effective stimulators in mixed lymphocyte reactions and can induce generation of cytotoxic T lymphocytes specific for autologous nonmodified leukemia cells. As such, Ad-CD154 can induce a host antileukemia response that may have therapeutic potential.

MeSH Terms
Adenoviridae/genetics Antigen Presentation/genetics Antigens, CD/immunology B-Lymphocytes/immunology CD40 Ligand Cytotoxicity Tests, Immunologic DNA, Complementary/genetics Flow Cytometry Gene Expression Gene Transfer Techniques Genetic Therapy/methods Genetic Vectors HeLa Cells Humans Immunity, Active/genetics Leukemia, Lymphocytic, Chronic, B-Cell/genetics,immunology Lymphocyte Culture Test, Mixed Membrane Glycoproteins/genetics,immunology Polymerase Chain Reaction Recombination, Genetic T-Lymphocytes, Cytotoxic/immunology Transcriptional Activation Tumor Cells, Cultured
Chemicals
Antigens, CD DNA, Complementary Membrane Glycoproteins CD40 Ligand
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kato K
Division of Hematology/Oncology, Department of Medicine and the UCSD Human Gene Therapy Program, UCSD School of Medicine, La Jolla, California 92093-0663, USA.
Cantwell M J
Sharma S
Kipps T J
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI1472
Published
1998-03-01
Pages
1133-41
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508665
Subset
IM
Grants
NCI NIH HHS · CA66000 · United States
NCI NIH HHS · R37-CA49870RO1 · United States
External Links
PubMed source DOI: 10.1172/JCI1472 PMC Full Text View journal details
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