Sanchez-Lugo Yessica E, Perez-Trujillo Jose J, Gutierrez-Puente Yolanda, Garcia-Garcia Aracely, Rodriguez-Rocha Humberto, Barboza-Quintana Oralia, Muñoz-Maldonado Gerardo E, Saucedo-Cardenas Odila, de Oca-Luna Roberto Montes, Loera-Arias Maria J
Departamento de Histologia, Facultad de Medicina, Universidad Autonoma de Nuevo Leon (UANL), Madero y Aguirre Pequeño s/n Mitras Centro, CP: 64665, Monterrey, NL, Mexico,
Biotechnol Lett. 2015 Apr;37(4):779-85. doi: 10.1007/s10529-014-1746-4. Epub 2014 Dec 17.
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.
融合细胞因子是由两种细胞因子融合形成的蛋白质。它们比单个细胞因子或不同细胞因子的组合具有更高的生物利用度和治疗潜力。干扰素γ诱导蛋白10（CXCL10）和淋巴细胞趋化因子（XCL1）是细胞因子趋化家族的成员，它们通过引发免疫系统细胞趋化来诱导肿瘤消退。我们构建了一种表达CXCL10/XCL1融合细胞因子的复制缺陷型腺病毒系统（Ad FIL），并在体外和体内评估了其趋化反应。在体外，CXCL10/XCL1融合细胞因子在IL-2刺激的淋巴细胞中比单个或联合细胞因子引发了更大的趋化作用。CXCL10/XCL1融合细胞因子的生物活性在体内通过CXCR3+细胞的肿瘤内化学吸引得到证实。因此，这种新型的CXCL10/XCL1融合细胞因子可能代表一种用于癌症和其他需要触发免疫系统细胞募集的疾病的基因治疗的潜在工具。
