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CXCL10/XCL1 fusokine elicits in vitro and in vivo chemotaxis
Authors:Yessica E. Sanchez-Lugo  Jose J. Perez-Trujillo  Yolanda Gutierrez-Puente  Aracely Garcia-Garcia  Humberto Rodriguez-Rocha  Oralia Barboza-Quintana  Gerardo E. Muñoz-Maldonado  Odila Saucedo-Cardenas  Roberto Montes de Oca-Luna  Maria J. Loera-Arias
Affiliation:1.Departamento de Histologia, Facultad de Medicina,Universidad Autonoma de Nuevo Leon (UANL),Monterrey,Mexico;2.Departamento de Bioquimica, Facultad de Ciencias Biologicas,Universidad Autonoma de Nuevo Leon (UANL),Monterrey,Mexico;3.Servicio de Anatomia Patologica y Citopatologia, Hospital Universitario “Dr. Jose Eleuterio Gonzalez” de la Facultad de Medicina,Universidad Autonoma de Nuevo Leon (UANL),Monterrey,Mexico;4.Servicio de Cirugia General, Hospital Universitario “Dr. Jose Eleuterio González” de la Facultad de Medicina,Universidad Autonoma de Nuevo Leon (UANL),Monterrey,Mexico;5.Division de Genética, Centro de Investigacion Biomedica del Noreste,Instituto Mexicano del Seguro Social (IMSS),Monterrey,Mexico
Abstract:Fusokines are proteins formed by the fusion of two cytokines. They have greater bioavailability and therapeutic potential than individual cytokines or a combination of different cytokines. Interferon-gamma-inducible protein 10 (CXCL10) and lymphotactin (XCL1) are members of the chemotactic family of cytokines, which induce tumor regression by eliciting immune-system cell chemotaxis. We engineered a replication-deficient adenoviral system expressing CXCL10/XCL1 fusokine (Ad FIL) and assessed its chemotactic response in vitro and in vivo. The CXCL10/XCL1 fusokine elicited a greater chemotactic effect in IL-2 stimulated lymphocytes than individual or combined cytokines in vitro. CXCL10/XCL1 fusokine biological activity was demonstrated in vivo by intratumoral chemoattraction of CXCR3+ cells. Thus, this novel CXCL10/XCL1 fusokine may represent a potential tool for gene therapy treatment of cancer and other illnesses that require triggering immune-system cell recruitment.
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