Immunofilaments Are Well Tolerated after Local or Systemic Administration in Mice

免疫丝蛋白在小鼠局部或全身给药后均具有良好的耐受性

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作者:Lea Weiss ,René Classens ,Marjolein Schluck ,Emilia Grad ,Yusuf Dölen ,Lieke van der Woude ,Dominique van Midden ,Lisa Maassen ,Kiek Verrijp ,Koen van Riessen ,Eric van Dinther ,Philipp M Hagemann ,Carl G Figdor ,Roel Hammink

Abstract

The invention of nanosized biomaterials has paved the way for novel therapeutics that can manipulate cells on a nanoscale. Nanosized immunofilaments (IFs) are synthetic filamentous polymers consisting out of polyisocyanopeptides, which have been recently established as a powerful platform to activate specific immune cells in vivo such that they raise an antitumor immune response. However, toxicological effects or immunogenicity toward the IFs have not yet been investigated. In this study, we evaluated potential toxic or immunogenic effects in C57BL/6 mice upon intravenous or subcutaneous injection of nonfunctionalized IFs or immunostimulatory IFs over 30 days. We here present a detailed analysis of the gross pathology, hematological parameters, blood biochemistry, histology, and antibody-response against the IF backbone. Our results demonstrate that IFs do not induce severe acute or chronic toxicity in mice. After 30 days, we only found elevated IgG-titers in intravenously injected but not subcutaneously injected mice. In summary, we demonstrate that IFs can be administered into a living organism without adverse side effects, thereby establishing the safety of IFs as a therapeutic intervention.

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