In vitro models for immunogenicity prediction of therapeutic proteins

Groell, Floriane; Jordan, Olivier; Borchard, Gerrit

doi:10.1016/j.ejpb.2018.06.008

Cited by 35 publications

(17 citation statements)

References 150 publications

(156 reference statements)

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“…Cell culture models are fundamental instruments for basic to translational research, in particular for cancer 24,25 . Although in vitro conditions do not exactly replicate in vivo situations, their role remains important 3 .…”

Section: Discussionmentioning

confidence: 99%

A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology

Candini¹,

Grisendi²,

Foppiani³

et al. 2019

Sci Rep

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Tumors develop within complex cell-to-cell interactions, with accessory cells playing a relevant role starting in the early phases of cancer progression. This event occurs in a three-dimensional (3D) environment, which to date, has been difficult to reproduce in vitro due to its complexity. While bi-dimensional cultures have generated substantial data, there is a progressive awareness that 3D culture strategies may rapidly increase the understanding of tumor development and be used in anti-cancer compound screening and for predicting response to new drugs utilizing personalized approaches. However, simple systems capable of rapidly rebuilding cancer tissues ex-vivo in 3D are needed and could be used for a variety of applications. Therefore, we developed a flat, handheld and versatile 3D cell culture bioreactor that can be loaded with tumor and/or normal cells in combination which can be monitored using a variety of read-outs. This biocompatible device sustained 3D growth of tumor cell lines representative of various cancers, such as pancreatic and breast adenocarcinoma, sarcoma, and glioblastoma. The cells repopulated the thin matrix which was completely separated from the outer space by two gas-permeable membranes and was monitored in real-time using both microscopy and luminometry, even after transportation. The device was tested in 3D cytotoxicity assays to investigate the anti-cancer potential of chemotherapy, biologic agents, and cell-based therapy in co-cultures. The addition of luciferase in target cancer cells is suitable for comparative studies that may also involve parallel in vivo investigations. Notably, the system was challenged using primary tumor cells harvested from lung cancer patients as an innovative predictive functional assay for cancer responsiveness to checkpoint inhibitors, such as nivolumab. This bioreactor has several novel features in the 3D-culture field of research, representing a valid tool useful for cancer investigations, drug screenings, and other toxicology approaches.

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Section: Discussionmentioning

confidence: 99%

A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology

Candini¹,

Grisendi²,

Foppiani³

et al. 2019

Sci Rep

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“…Also, it is important to mention that the resistance of specific protein domains to digestion is not the only condition for exerting an immunological response. Protein allergenicity during/after gastrointestinal digestion could increase due to the creation of neoepitopes resulting from native state protein digestion, or due to the increase in epitope concentration and their affinity to immune system cells (e.g., B cells) (Groell, Jordan, & Borchard, 2018). Moreover, digestion induced conformational changes (e.g.…”

Section: Digestibilitymentioning

confidence: 99%

Emergent food proteins – Towards sustainability, health and innovation

Fasolin

Pereira

Pinheiro

et al. 2019

Food Research International

178

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There is an increasing demand for alternative and sustainable protein sources, such as vegetables, insects and microorganisms, that can meet the nutritional and sensory pleasantness needs of consumers. This emergent interest for novel protein sources, allied with "green" and cost-effective processing technologies, such as high hydrostatic pressure, ohmic heating and pulsed electric fields, can be used as strategies to improve the consumption of proteins from sustainable sources without compromising food security. In addition to their nutritional value, these novel proteins present several technological-functional properties that can be used to create various protein systems in different scales (i.e., macro, micro and nano scale), which can be tailored for a specific application in innovative food products. However, in order for these novel protein sources to be broadly used in future food products, their fate in the human gastrointestinal tract (e.g., digestion and bioavailability) must be assessed, as well as their safety for consumers must be clearly demonstrated. In particular, these proteins may become novel allergens triggering adverse reactions and, therefore, a comprehensive allergenicity risk assessment is needed. This review presents an overview of the most promising alternative protein sources, their application in the production of innovative food systems, as well as their potential effects on human health. In addition, new insights on sustainable processing strategies are given.

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“…Despite their best efforts, it is often necessary for sponsors to implement strategies to mitigate unintended immune responses once drugs have progressed into the clinic. In some cases, this need may be anticipated given historical experience with the therapeutic class, or other knowledge/experience gathered in preclinical development through a growing number of in silico and in vitro methods [39,83,84] (although generally not animal toxicology studies for the reasons described previously). However, in many cases, the full nature of these responses cannot be understood until after the candidate enters clinical trials, and even then, limited subject numbers and the potential for substantial inter-subject variability from both genetic and non-genetic factors can make it difficult to get a full understanding of impact prior the initiation of pivotal studies [12,21,85].…”

Section: Clinical Management and Treatment Of Immune Responsesmentioning

confidence: 99%

Regulatory and strategic considerations for addressing immunogenicity and related responses in biopharmaceutical development programs

Vandivort

Horton

Johnson

2020

J. Clin. Trans. Sci.

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The last three decades have seen the biotherapeutic drug market evolve from promising concept to market dominance in a range of clinical indications. This growth has been spurred by the success of established drug classes like monoclonal antibodies, but also by the introduction of biosimilars, and more recently, multiple novel cell and gene therapies. Biotherapeutic drug development presents many unique challenges, but unintended immune responses are among the most common reasons for program attrition. Anti-drug antibodies can impact the safety and efficacy of drug products, and related immune responses, like the cytokine release syndrome that occurred in the infamous TGN-1412 clinical trial, can be challenging to predict with nonclinical models. For this reason, it is important that development programs proceed with a scientifically grounded and measured approach to these responses. This process begins at the discovery stage with the application of “quality by design,” continues into the clinic with the development of quality assays and management strategies, and culminates in the effective presentation of this information in regulatory documents. This review provides an overview of some of the key strategic and regulatory considerations for biotherapeutics as they pertain to immunogenicity and related responses.

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In vitro models for immunogenicity prediction of therapeutic proteins

Cited by 35 publications

References 150 publications

A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology

A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology

Emergent food proteins – Towards sustainability, health and innovation

Regulatory and strategic considerations for addressing immunogenicity and related responses in biopharmaceutical development programs

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