Breij Esther C W, Batenburg Joseph J
Utrecht University, Department of Biochemistry and Cell Biology, Veterinary Sciences Faculty, Yalelaan 2, 3584 CM Utrecht, The Netherlands.
Expert Opin Biol Ther. 2008 Apr;8(4):409-19. doi: 10.1517/14712598.8.4.409.
Drug-resistant pathogens are an increasing threat, particularly for hospitalised patients. In search of a new approach in pathogen targeting, we developed bifunctional proteins that combine broad spectrum pathogen recognition with efficient targeting to phagocytes. Pathogen recognition is provided by a recombinant fragment of surfactant protein D (rfSP-D) while targeting to phagocytic cells is accomplished by coupling rfSP-D to F(ab') fragments directed against Fcalpha receptor I (FcalphaRI) or Fcgamma receptor I (FcgammaRI). FcalphaRI and FcgammaRI are expressed on myeloid cells, and induce rapid internalisation of particles after crosslinking.
OBJECTIVE/METHODS: In this review we discuss the roles of SP-D and Fc receptors in host defence as a rationale for rfSP-D/anti-FcR bifunctional proteins. Furthermore we summarise the available data on rfSP-D/anti-FcR proteins as well as opportunities and considerations for future use of such bifunctional proteins.
RESULTS/CONCLUSION: rfSP-D/anti-FcR bifunctional proteins could be of great value for the treatment of a variety of infectious diseases. The focus in the near future should be on proof-of-principle by testing the bifunctional proteins in different mouse models of infectious disease.
耐药病原体构成的威胁日益增加，对住院患者而言尤为如此。为了寻找一种针对病原体的新方法，我们开发了双功能蛋白，该蛋白将广谱病原体识别与有效靶向吞噬细胞相结合。病原体识别由表面活性蛋白D的重组片段（rfSP-D）提供，而靶向吞噬细胞则通过将rfSP-D与针对Fcα受体I（FcαRI）或Fcγ受体I（FcγRI）的F（ab'）片段偶联来实现。FcαRI和FcγRI在髓样细胞上表达，并在交联后诱导颗粒的快速内化。
目的/方法：在本综述中，我们讨论了SP-D和Fc受体在宿主防御中的作用，以此作为rfSP-D/抗FcR双功能蛋白的理论依据。此外，我们总结了关于rfSP-D/抗FcR蛋白的现有数据，以及此类双功能蛋白未来应用的机会和注意事项。
结果/结论：rfSP-D/抗FcR双功能蛋白可能对多种传染病的治疗具有重要价值。在不久的将来，重点应放在通过在不同的传染病小鼠模型中测试双功能蛋白来进行原理验证上。
