title: Sindbis viral vectors target hematopoietic malignant cells.
abstract: Sindbis viral vectors target and inhibit the growth of various solid tumors in mouse models. However, their efficacy against blood cancer has not been well established. Here, we show that Sindbis vectors infect and efficiently trigger apoptosis in mouse BW5147 malignant hematopoietic T-cells, but only at low levels in human lymphoma and leukemia cells (Jurkat, Karpas, CEM, DHL and JB). The Mr 37/67 kD laminin receptor (LAMR) has been suggested to be the receptor for Sindbis virus. However, JB cells, which are infected by Sindbis at low efficiency, express high levels of LAMR, revealing that additional factors are involved in Sindbis tropism. To test the infectivity and therapeutic efficacy of Sindbis vectors against malignant hematopoietic cells in vivo, we injected BW5147 cells intraperitoneally into (C3HXAKR) F1 hybrid mice. We found that Sindbis vectors targeted the tumors and significantly prolonged survival of tumor-bearing mice. We also tested the Sindbis vectors in a transgenic CD4-Rgr model, which spontaneously develop thymic lymphomas. However, infectivity in this model was less efficient. Taken together, these results demonstrate that Sindbis vectors have the potential to target and kill hematopoietic malignancies in mice, but further research is needed to evaluate the mechanism underlining the susceptibility of human lymphoid malignancies to Sindbis therapy.
authors.affiliation: Department of Pathology and NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. Rafi.suzme@nyumc.org
authors.forename: R
authors.initials: R
authors.lastname: Suzme
authors.forename: J-C
authors.initials: JC
authors.lastname: Tseng
authors.forename: B
authors.initials: B
authors.lastname: Levin
authors.forename: S
authors.initials: S
authors.lastname: Ibrahim
authors.forename: D
authors.initials: D
authors.lastname: Meruelo
authors.forename: A
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism; D017209:Apoptosis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007274:Injections, Intraperitoneal; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000628:therapy*; D050130:Oncolytic Virotherapy; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism; D012845:Sindbis Virus / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D017474:Receptors, Laminin; C016658:phorbolol myristate acetate; D013755:Tetradecanoylphorbol Acetate