In vitro assays for effector T cell functions and activity of immunomodulatory antibodies Journal Article


Authors: Zappasodi, R.; Budhu, S.; Abu-Akeel, M.; Merghoub, T.
Article Title: In vitro assays for effector T cell functions and activity of immunomodulatory antibodies
Abstract: The recent clinical success of cancer immunotherapy with checkpoint blockade has led to renewed interest into the development of immune modulatory agents with the capacity to activate anti-tumor T cell responses. Standardization of optimized in vitro assays for efficient assessment of immune function of such new drugs is thus needed to facilitate clinical development of the optimal drug candidates. Here, we describe an optimized version of T cell suppression assay designed to test the effect of immunomodulatory agents on T cell function and activation. We apply this assay to investigate the agonist activity of the T cell co-stimulatory molecule glucocorticoid-induced TNFR-related protein (GITR). We detail a protocol for concurrent assessment of multiple levels of T cell functional modulation upon GITR engagement, including T cell priming, activation and effector function, in a single assay. As human GITR agonist antibodies are currently under development, availability of standardized cell-based functional assays of GITR agonism is instrumental to translate anti-GITR therapy into the clinical setting. © 2020 Elsevier Inc.
Keywords: t cells; immunotherapy; co-stimulation; gitr; immune suppression; tregs
Journal Title: Methods in Enzymology
Volume: 631
ISSN: 0076-6879
Publisher: Academic Press  
Date Published: 2020-01-01
Start Page: 43
End Page: 59
Language: English
DOI: 10.1016/bs.mie.2019.08.012
PUBMED: 31948562
PROVIDER: scopus
PMCID: PMC7362725
DOI/URL:
Notes: Chapter 3 as "Tumor Immunology and Immunotherapy - Cellular Methods Part A" (ISBN: 978-0-12-818673-2) -- Source: Scopus
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  1. Taha Merghoub
    364 Merghoub
  2. Sadna Budhu
    86 Budhu