Enhancement of specific cellular immune response induced by glycosyl-phosphatidylinositol-anchored BCR/ABL and mIL-12.
bcr/abl fusion gene is thought to be a promising target for chronic myelogenous leukemia (CML) patients to enhance immune response after attaining complete remission. In this study, we sought to enhance cellular immunity by co-expression of BCR/ABL and murine IL-12 gene on the tumor cell surface as a glycosyl-phosphatidylinositol (GPI)-form. The successfully constructed plasmid pBudCE4.1-BCR/ABL-GPI-mIL12 resulted in high levels of splenocyte proliferative responses, significant levels of IL-2 and IFNγ, and strong cytotoxic T-lymphocyte (CTL) responses in vitro. In a murine transplant model, the vaccinated mice showed decreased infiltration of leukemia cells and reduced expression of BCR/ABL transcripts and protein in bone marrow cells. Results of the present study indicated that this novel immunization strategy is useful in enhancing immune protection in mice, which would provide new insights into the development of effective vaccines for treating CML.
Department of Immunology, Molecular Medicine and Cancer Research, Chongqing Medical University, Chongqing, China.
Kun
K
Tao
Ya-Juan
YJ
Li
Dong
D
Wang
Jie-Yu
JY
Qi
Yi-Ping
YP
Deng
Hai-Xia
HX
Wang
Jing
J
Hu
Wen-Li
WL
Feng
D000818:Animals; D016026:Bone Marrow Transplantation; D019556:COS Cells; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D007111:Immunity, Cellular / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D014162:Transfection
D019496:Cancer Vaccines; D016207:Cytokines; D017261:Glycosylphosphatidylinositols; D018664:Interleukin-12; D016044:Fusion Proteins, bcr-abl