Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells.
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.
Kato
K
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
MJ
Sharma
S
S
Kipps
T J
TJ
D000256:Adenoviridae / Q000235:genetics; D017951:Antigen Presentation / Q000235:genetics; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand; D003601:Cytotoxicity Tests, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D007110:Immunity, Active / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D023201:CD40 Ligand