Methods for Analysis of Nanoparticle Immunosuppressive Properties In Vitro and In Vivo.

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  • Additional Information
    • Source:
      Publisher: Humana Press Country of Publication: United States NLM ID: 9214969 Publication Model: Print Cited Medium: Internet ISSN: 1940-6029 (Electronic) Linking ISSN: 10643745 NLM ISO Abbreviation: Methods Mol Biol Subsets: MEDLINE
    • Publication Information:
      Publication: Totowa, NJ : Humana Press
      Original Publication: Clifton, N.J. : Humana Press,
    • Subject Terms:
      Antibody Formation* ; Immunity, Cellular*; Immunosuppressive Agents/*adverse effects ; Leukocytes/*immunology ; Nanoparticles/*adverse effects; Animals ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; Humans ; Immunosuppression Therapy ; Leukocytes/cytology ; Male ; Mice ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology
    • Abstract:
      Adverse drug effects on the immune system function represent a significant concern in the pharmaceutical industry, because 10-20% of the drug withdrawal from the market is accounted to immunotoxicity. Immunosuppression is one such adverse effect. The traditional immune function test used to estimate materials' immunosuppression is a T-cell-dependent antibody response (TDAR). This method involves a 28 day in vivo study evaluating the animal's antibody titer to a known antigen (KLH) with and without challenge. Due to the limited quantities of novel drug candidates, an in vitro method called human leukocyte activation (HuLa) assay has been developed to substitute the traditional TDAR assay during early preclinical development. In this test, leukocytes isolated from healthy donors vaccinated with the current year's flu vaccine are incubated with Fluzone in the presence or absence of a test material. The antigen-specific leukocyte proliferation is then measured by ELISA analyzing incorporation of BrdU into DNA of the proliferating cells. Here, we describe the experimental procedures for investigating immunosuppressive properties of nanoparticles by both TDAR and HuLa assays, discuss the in vitro-in vivo correlation of these methods, and show a case study using the iron oxide nanoparticle formulation, Feraheme.
    • Grant Information:
      HHSN261200800001E United States CA NCI NIH HHS
    • Contributed Indexing:
      Keywords: Antigen; Immunosuppression; Leukocyte proliferation; Nanoparticles; TDAR
    • Accession Number:
      0 (Immunosuppressive Agents)
    • Publication Date:
      Date Created: 20171018 Date Completed: 20180529 Latest Revision: 20211204
    • Publication Date:
      20221213
    • Accession Number:
      10.1007/978-1-4939-7352-1_14
    • Accession Number:
      29039101