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Antidrug Antibody Formation in Oncology: Clinical Relevance and Challenges.

作者信息

van Brummelen Emilie M J, Ros Willeke, Wolbink Gertjan, Beijnen Jos H, Schellens Jan H M

机构信息

Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Immunopathology, Sanquin Research, Amsterdam, The Netherlands Reade Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands.

出版信息

Oncologist. 2016 Oct;21(10):1260-1268. doi: 10.1634/theoncologist.2016-0061. Epub 2016 Jul 20.


DOI:10.1634/theoncologist.2016-0061
PMID:27440064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5061540/
Abstract

UNLABELLED: : In oncology, an increasing number of targeted anticancer agents and immunotherapies are of biological origin. These biological drugs may trigger immune responses that lead to the formation of antidrug antibodies (ADAs). ADAs are directed against immunogenic parts of the drug and may affect efficacy and safety. In other medical fields, such as rheumatology and hematology, the relevance of ADA formation is well established. However, the relevance of ADAs in oncology is just starting to be recognized, and literature on this topic is scarce. In an attempt to fill this gap in the literature, we provide an up-to-date status of ADA formation in oncology. In this focused review, data on ADAs was extracted from 81 clinical trials with biological anticancer agents. We found that most biological anticancer drugs in these trials are immunogenic and induce ADAs (63%). However, it is difficult to establish the clinical relevance of these ADAs. In order to determine this relevance, the possible effects of ADAs on pharmacokinetics, efficacy, and safety parameters need to be investigated. Our data show that this was done in fewer than 50% of the trials. In addition, we describe the incidence and consequences of ADAs for registered agents. We highlight the challenges in ADA detection and argue for the importance of validating, standardizing, and describing well the used assays. Finally, we discuss prevention strategies such as immunosuppression and regimen adaptations. We encourage the launch of clinical trials that explore these strategies in oncology. IMPLICATIONS FOR PRACTICE: Because of the increasing use of biologicals in oncology, many patients are at risk of developing antidrug antibodies (ADAs) during therapy. Although clinical consequences are uncertain, ADAs may affect pharmacokinetics, patient safety, and treatment efficacy. ADA detection and reporting is currently highly inconsistent, which makes it difficult to evaluate the clinical consequences. Standardized reporting of ADA investigations in the context of the aforementioned parameters is critical to understanding the relevance of ADA formation for each drug. Furthermore, the development of trials that specifically aim to investigate clinical prevention strategies in oncology is needed.

摘要

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本文引用的文献

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Front Immunol. 2014-10-20

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Med Oncol. 2014-12

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