Adenovirus transduction to effect CD40 signalling improves the immune stimulatory activity of myeloma cells.
Neoplastic plasma cells from patients with myeloma fail to stimulate an effective anti-myeloma immune response, which may be in part due to their deficient expression of immune accessory molecules. Attempting to alter this, we infected myeloma cell lines and patient-derived primary myeloma cells with an adenovirus encoding CD154 (Ad-CD154). Myeloma cells were made to express the CD154 transgene at multiplicity of infection (MOI) between 10 and 1000. Furthermore, infection of CD40(positive) myeloma cells with Ad-CD154, but not an adenovirus encoding an irrelevant transgene, beta-galactosidase (Ad-LacZ), induced enhanced expression of immune accessory molecules, such as CD54, HLA-DR and CD70. In addition, Ad-CD154-infected myeloma cells could activate bystander CD40(positive) antigen-presenting cells to express immune accessory molecules. Consequently, Ad-CD154 infected myeloma cells stimulated proliferation in allogeneic mixed lymphocyte reactions (MLR). Finally, co-infection of CD40(negative) myeloma cells with Ad-CD154 and an adenovirus encoding CD40 (Ad-CD40) induced expression of immune accessory molecules and enhanced the MLR stimulatory capacity of transduced myeloma cells. Collectively, these results indicate that infection of myeloma cells with Ad-CD154 or Ad-CD154/Ad-CD40 can induce changes in myeloma cells that enhance their ability to induce cellular immune activation. As such, this approach may have potential application for immune therapy of patients with this disease.
Division of Blood and Marrow Transplantation, Department of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0663, USA.
Asad
A
Bashey
Mark J
MJ
Cantwell
Thomas J
TJ
Kipps
D000256:Adenoviridae; D000257:Adenoviridae Infections / Q000276:immunology; D001854:Bone Marrow Cells / Q000473:pathology; D019013:CD40 Antigens / Q000276:immunology*; D002455:Cell Division; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D014161:Transduction, Genetic / Q000379:methods; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens