An anti-TNF-alpha antibody mimetic to treat ocular inflammation

作者：Khalili Hanieh; Lee Richard W; Khaw Peng T; Brocchini Steve^*; Dick Andrew D^*; Copland David A

来源：Scientific Reports, 2016, 6(1): 36905.

DOI：10.1038/srep36905

Infliximab is an antibody that neutralizes TNF-alpha and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpF(infliximab)) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpF(infliximab) was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpF(infliximab) maintained binding affinity for both human and murine recombinant TNF-alpha. No Fc mediated RPE cellular uptake was observed for FpF(infliximab). Both Infliximab and FpF(infliximab) suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells in the EAU mice after a single intravitreal injection at the onset of peak disease. These results offer an opportunity to develop and formulate for ocular use, FpF molecules designed for single and potentially multiple targets using bi-specific FpFs.

• 出版日期2016-11-22