Quantifying Antigen-Specific T Cell Responses When Using Antigen-Agnostic Immunotherapies

Molecular Therapy. Methods & Clinical Development
Jacob P van VlotenByram W Bridle

Abstract

Immunotherapies are at the forefront of the fight against cancers, and researchers continue to develop and test novel immunotherapeutic modalities. Ideal cancer immunotherapies induce a patient's immune system to kill their own cancer and develop long-lasting immunity. Research has demonstrated a critical requirement for CD8+ and CD4+ T cells in achieving durable responses. In the path to the clinic, researchers require robust tools to effectively evaluate the capacity for immunotherapies to generate adaptive anti-tumor responses. To study functional tumor-specific T cells, researchers have relied on targeting tumor-associated antigens (TAAs) or the inclusion of surrogate transgenes in pre-clinical models, which facilitate detection of T cells by using the targeted antigen(s) in peptide re-stimulation or tetramer-staining assays. Unfortunately, many pre-clinical models lack a defined TAA, and epitope mapping of TAAs is costly. Surrogate transgenes can alter tumor engraftment and influence the immunogenicity of tumors, making them less relevant to clinical tumors. Further, some researchers prefer to develop therapies that do not rely on pre-defined TAAs. Here, we describe a method to exploit major histocompatibility complex expr...Continue Reading

Citations

Dec 4, 2020·Journal for Immunotherapy of Cancer·Siwen Hu-LieskovanHolden T Maecker
Feb 22, 2021·Drug Delivery and Translational Research·Anvay UkidveSamir Mitragotri
Apr 8, 2021·British Journal of Cancer·Maximilian BoeschMartin H Brutsche
Aug 12, 2021·Nature Reviews. Cancer·Roman M ChabanonSophie Postel-Vinay

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Methods Mentioned

BETA
flow cytometry
FACS
Flow
Assay
PMA
transfection

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