Genetically modified myeloma cell vaccine inducing antitumor immune response in vivo.
This study was aimed to evaluate the in vivo antitumor effect of genetically modified myeloma cell vaccine on human myeloma xenografts implanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Human immune system was established in NOD/SCID mice by intraperitoneal injection of human peripheral blood lymphocytes (PBLs). After being inoculated subcutaneously with irradiated myeloma cell line sko-007, adenovirally transferred with GFP or p53, granulocyte-macrophage colony-stimulating factor (GM-CSF) and B7-1 genes, huPBL-NOD/SCID mice were challenged by subcutaneous injection of non-transferred sko-007 cells. The results indicated that Ad-p53/GM-CSF/B7-1-infected sko-007 cell vaccination significantly reduced local tumor growth compared with controls. Histopathological and immunohistochemical analysis showed that tumor tissues increasingly displayed diffuse necrosis, mainly caused by apoptosis, accompanied with significant fibroplasias and blood vessel hyperplasia, and human T cells infiltrated into the tumor tissues. It is concluded that transgenic p53, GM-CSF and B7-1 expression produces an immune response against myeloma cells and may be of therapeutic value for multiple myeloma in human being.
Ren
Su-Ping
SP
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Wang
Li-Sheng
LS
Guo
Qiang
Q
Wang
Hua
H
Jia
Xiang-Xu
XX
Xu
Juan
J
Wang
Heng-Xiang
HX
Wu
Chu-Tse
CT
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D016158:Genes, p53 / Q000276:immunology; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D007167:Immunotherapy; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology*; D009368:Neoplasm Transplantation
D018122:B7-1 Antigen; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor