title: A novel strategy inducing autophagic cell death in Burkitt's lymphoma cells with anti-CD19-targeted liposomal rapamycin.
abstract: Relapsed or refractory Burkitt's lymphoma often has a poor prognosis in spite of intensive chemotherapy that induces apoptotic and/or necrotic death of lymphoma cells. Rapamycin (Rap) brings about autophagy, and could be another treatment. Further, anti-CD19-targeted liposomal delivery may enable Rap to kill lymphoma cells specifically. Rap was encapsulated by anionic liposome and conjugated with anti-CD19 antibody (CD19-GL-Rap) or anti-CD2 antibody (CD2-GL-Rap) as a control. A fluorescent probe Cy5.5 was also liposomized in the same way (CD19 or CD2-GL-Cy5.5) to examine the efficacy of anti-CD19-targeted liposomal delivery into CD19-positive Burkitt's lymphoma cell line, SKW6.4. CD19-GL-Cy5.5 was more effectively uptaken into SKW6.4 cells than CD2-GL-Cy5.5 in vitro. When the cells were inoculated subcutaneously into nonobese diabetic/severe combined immunodeficiency mice, intravenously administered CD19-GL-Cy5.5 made the subcutaneous tumor fluorescent, while CD2-GL-Cy5.5 did not. Further, CD19-GL-Rap had a greater cytocidal effect on not only SKW6.4 cells but also Burkitt's lymphoma cells derived from patients than CD2-GL-Rap in vitro. The specific toxicity of CD19-GL-Rap was cancelled by neutralizing anti-CD19 antibody. The survival period of mice treated with intravenous CD19-GL-Rap was significantly longer than that of mice treated with CD2-GL-Rap after intraperitoneal inoculation of SKW6.4 cells. Anti-CD19-targeted liposomal Rap could be a promising lymphoma cell-specific treatment inducing autophagic cell death.
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: K
authors: K
authors: Ono
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: T
authors: T
authors: Sato
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: S
authors: S
authors: Iyama
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: A
authors: A
authors: Tatekoshi
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: A
authors: A
authors: Hashimoto
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Y
authors: Y
authors: Kamihara
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: H
authors: H
authors: Horiguchi
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: S
authors: S
authors: Kikuchi
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Y
authors: Y
authors: Kawano
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: K
authors: K
authors: Takada
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: T
authors: T
authors: Hayashi
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: K
authors: K
authors: Miyanishi
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Y
authors: Y
authors: Sato
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: R
authors: R
authors: Takimoto
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: M
authors: M
authors: Kobune
authors: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: J
authors: J
authors: Kato