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

Autor: van Vloten JP; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada., Santry LA; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada., McAusland TM; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada., Karimi K; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada., McFadden G; The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA., Petrik JJ; Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada., Wootton SK; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada., Bridle BW; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
Jazyk: angličtina
Zdroj: Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2019 Jan 29; Vol. 13, pp. 154-166. Date of Electronic Publication: 2019 Jan 29 (Print Publication: 2019).
DOI: 10.1016/j.omtm.2019.01.012
Abstrakt: 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.
Databáze: MEDLINE