%0 Journal Article
%T Immunogenicity and Immune Complex Disease in Preclinical Safety Studies
%A John L. Vahle
%J Toxicologic Pathology
%@ 1533-1601
%D 2018
%R 10.1177/0192623318797070
%X This article summarizes a continuing education presentation on immunogenicity that was part of a continuing education course entitled, ˇ°Clinical Pathology of Biotherapeutics.ˇ± Immunogenicity of a biotherapeutic can have diverse impacts including altered systemic exposure and pharmacologic responses and, in a fraction of the cases, safety concerns including cross-reactive neutralization of endogenous proteins or sequela related to immune complex disease (ICD). In most cases, immune complexes are readily cleared from circulation; however, based on physiochemical properties, insoluble complexes form, activate complement, and deposit in tissues. Using published information and personal experience, a set of repeat-dose monkey toxicity studies with manifestations suggestive of ICD was reviewed to summarize the spectrum of clinical and pathology findings. The most common live-phase observation linked to ICD was an acute postdosing reaction following multiple dose administrations characterized by generalized collapse and attributed to acute complement activation. Less common live-phase observations were related to syndromes such as a consumptive coagulopathy or a protein losing nephropathy. The most common histologic change attributed to ICD was multi-organ vascular/perivascular inflammation followed by glomerulonephritis. The presentation concluded with a description of the challenges in assessing the relevance of immunogenicity-related reaction in monkey to human clinical use
%K immunogenicity
%K toxicity
%K immune complex disease
%K nonhuman primate
%K biotherapeutics
%U https://journals.sagepub.com/doi/full/10.1177/0192623318797070