Aggregation, immune complexes and immunogenicity

Immunogenicity of Isogenic IgG in Aggregates and Immune Complexes

A paradox in monoclonal antibody (mAb) therapy is that despite the well-documented tolerogenic properties of deaggregated IgG, most therapeutic IgG mAb induce anti-mAb responses. To analyze CD4 T cell reactions against IgG in various physical states, we developed an adoptive transfer model using CD4+ T cells specific for a Vκ region-derived peptide in the hapten-specific IgG mAb 36-71. We found...

Immunogenicity to Biotherapeutics – The Role of Anti-drug Immune Complexes

Biological molecules are increasingly becoming a part of the therapeutics portfolio that has been either recently approved for marketing or those that are in the pipeline of several biotech and pharmaceutical companies. This is largely based on their ability to be highly specific relative to small molecules. However, by virtue of being a large protein, and having a complex structure with struct...

Mechanisms Underlying Aggregation Induced Immunogenicity

Cationic Immune Stimulating Complexes Containing Soluble Leishmania Antigens: Preparation, Characterization and in Vivo Immune Response Evaluation

Background: Cationic immune stimulating complexes (PLUSCOMs) are particulate antigen delivery systems. PLUSCOMs consist of cationic immunostimulatory complexes (ISCOMs) derivatives and are able to elicit in vivo T cell responses against an antigen. Objective: To evaluate the effects of PLUSCOMs containing Leishmaniamajor antigens (SLA) on the type of immune response generated in the murine mod...

Immunogenicity of therapeutic proteins: Influence of aggregation

The elicitation of anti-drug antibodies (ADA) against biotherapeutics can have detrimental effects on drug safety, efficacy, and pharmacokinetics. The immunogenicity of biotherapeutics is, therefore, an important issue. There is evidence that protein aggregation can result in enhanced immunogenicity; however, the precise immunological and biochemical mechanisms responsible are poorly defined. I...