Emerging biomarkers during clinical development of anti-CTLA4 antibody therapy Book Section


Authors: Ku, G. Y.; Kyi, C.; Yuan, J.
Editor: Rezaei, N.
Article/Chapter Title: Emerging biomarkers during clinical development of anti-CTLA4 antibody therapy
Abstract: Ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen 4 (CTLA4), was approved by the US Food and Drug Administration for advanced melanoma. However, only a subset of patients benefit, often with delayed radiographic response and at the expense of immune-related toxicity. Biomarker studies provide a platform to analyze pharmacodynamic changes during ipilimumab treatment, elucidating potential mechanisms of action and identifying patients who are more likely to benefit and/or are at greatest risk of developing immune-related toxicities. A variety of immunological assays are currently available to monitor phenotypic changes in different immune cell populations (activated T cells, regulatory T cells, myeloid-derived suppressor cells) and assess antigen-specific responses, as well as to assess the functionality and gene expression profile of antigen-specific T cell populations. New tools and directions include the use of protein arrays, the evaluation of other inhibitory molecules like programmed death 1 (PD-1), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin mucin 3 (Tim-3), and the evaluation of immune response at the tumor site. Any promising biomarker will ultimately require validation in prospective clinical trials. In this chapter, we describe the progress of biomarker assay development in anti-CTLA4 trials and review putative biomarkers. We provide a forward-looking perspective on immune monitoring of anti-CTLA4 immunotherapy in the context of increasingly complex and effective combination therapies. © Springer-Verlag Berlin Heidelberg 2015.
Book Title: Cancer Immunology: Bench to Bedside Immunotherapy of Cancers
ISBN: 978-3-662-44945-5
Publisher: Springer Verlag  
Publication Place: Heidelberg, Germany
Date Published: 2015-01-01
Start Page: 427
End Page: 439
Language: English
DOI: 10.1007/978-3-662-44946-2_24
PROVIDER: scopus
DOI/URL:
Notes: Book chapter -- Export Date: 2 November 2015 -- Source: Scopus
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  1. Geoffrey Yuyat Ku
    231 Ku
  2. Jianda Yuan
    105 Yuan