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J Clin Invest. 1998 Mar 1;101(5):1133-41.

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

Author information

1
Division of Hematology/Oncology, Department of Medicine and the UCSD Human Gene Therapy Program, UCSD School of Medicine, La Jolla, California 92093-0663, USA.

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.

PMID:
9486984
PMCID:
PMC508665
DOI:
10.1172/JCI1472
[Indexed for MEDLINE]
Free PMC Article

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