PURPOSE OF REVIEW In the last decade, biologicals revolutionized rheumatology. An increasing number of patients benefit from biotherapeuticals. However, some patients do not respond to treatment and others lose their response after a certain time. Immunogenicity is one of the factors linked to secondary nonresponse but its clinical significance has remained controversial. RECENT FINDINGS In r...

A mechanistic, multiscale mathematical model of immunogenicity for therapeutic proteins was built by recapitulating key underlying known biological processes for immunogenicity. The model is able to simulate immune responses based on protein-specific antigenic properties (e.g., number of T-epitopes and their major histocompatibility complex (MHC)-II binding affinities) and host-specific immunol...

Numbers of biotherapeutic products in development have increased over past decade. Despite providing significant benefits to patients with unmet needs, almost all protein-based biotherapeutics could induce unwanted immunogenicity, which result in a loss of efficacy and/or increase the risk of adverse reactions, such as infusion reactions, anaphylaxis, and even life-threatening response to endog...

MOTIVATION Both modeling of antigen-processing pathway including major histocompatibility complex (MHC) binding and immunogenicity prediction of those MHC-binding peptides are essential to develop a computer-aided system of peptide-based vaccine design that is one goal of immunoinformatics. Numerous studies have dealt with modeling the immunogenic pathway but not the intractable problem of immu...

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among...

Biotherapeutic products (BTPs) are the fastest growing medicines in the pharmaceutical market. Despite their clinical success, the immunogenicity of BTPs continues to be a major concern. Assessment of immunogenicity as well as appropriate interpretation of immunogenicity data is therefore, of critical importance for defining safety profile of these products for the purpose of their licensure an...

T-cells have to recognize peptides presented on MHC molecules to be activated and elicit their effector functions. Several studies demonstrate that some peptides are more immunogenic than others and therefore more likely to be T-cell epitopes. We set out to determine which properties cause such differences in immunogenicity. To this end, we collected and analyzed a large set of data describing ...

Immunogenicity is a significant problem associated with protein therapeutics, but can be predicted in advance by in silico, in vitro, and in vivo tools, which can identifiy sequences within the therapeutic protein that, when processed by T-cells, elicit an immune response. Recent developments in T-cell-dependent immunology relating to the immunogenicity of therapeutic products include the descr...

background and aims: among the bacterial agents, the most common cause of diarrheal disease is entrotoxigenic escherichia coli. letal toxin b (ltb) subunit of lt toxin could induce six-month immunity. clostridium botulinum causes botulism disease. bont/a-hc toxin subunit could induce two years immunity against this disease. it seems that the immunogenicity potency of these two subunits may infl...

level: intermediate T he conclusion of this CMC Forum continued to focus on the latest developments in detection and characterization of protein aggregates (1). Afternoon sessions detailed the most recent experiments probing the role of protein aggregates in immunogenicity, with discussions on the best models to use and initial results. Topics included potential thresholds for immunogenicity, l...