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

Jacob P. van Vloten, Lisa A. Santry, Thomas M. McAusland, Khalil Karimi, Douglas McFadden, James J. Petrik, Sarah K. Wootton, Byram W. Bridle

Research output: Contribution to journalArticle

1 Scopus citations

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 expression on murine cancer cell lines in a co-culture assay to detect T cells responding to bulk, undefined, tumor antigens. This is a tool to support the preclinical evaluation of novel, antigen-agnostic immunotherapies.

Original languageEnglish (US)
Pages (from-to)154-166
Number of pages13
JournalMolecular Therapy - Methods and Clinical Development
Volume13
DOIs
StatePublished - Jun 14 2019

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

van Vloten, J. P., Santry, L. A., McAusland, T. M., Karimi, K., McFadden, D., Petrik, J. J., Wootton, S. K., & Bridle, B. W. (2019). Quantifying Antigen-Specific T Cell Responses When Using Antigen-Agnostic Immunotherapies. Molecular Therapy - Methods and Clinical Development, 13, 154-166. https://doi.org/10.1016/j.omtm.2019.01.012