Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/20141
Title: Isolation and characterization of NY-ESO-1-specific T cell receptors restricted on various MHC molecules.
Austin Authors: Bethune, Michael T;Li, Xiao-Hua;Yu, Jiaji;McLaughlin, Jami;Cheng, Donghui;Mathis, Colleen;Moreno, Blanca Homet;Woods, Katherine;Knights, Ashley J;Garcia-Diaz, Angel;Wong, Stephanie;Hu-Lieskovan, Siwen;Puig-Saus, Cristina;Cebon, Jonathan S ;Ribas, Antoni;Yang, Lili;Witte, Owen N;Baltimore, David
Affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095
Division of Hematology and Oncology, Department of Medicine, University of California, Los Angeles, CA 90095
Cancer Immunobiology Laboratory, Ludwig Institute for Cancer Research, Heidelberg, VIC 3084, Australia
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095
Molecular Biology Institute, University of California, Los Angeles, CA 90095
Cancer Immunobiology Laboratory, Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095
Department of Medicine, University of California, Los Angeles, CA 90095
Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, CA 90095
Issue Date: 6-Nov-2018
metadata.dc.date: 2018-10-22
Publication information: Proceedings of the National Academy of Sciences of the United States of America 2018; 115(45): E10702-E10711
Abstract: Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. Due to the prevalence of the HLA-A2 MHC class I supertype in most human populations, the majority of TCR gene therapy trials targeting public antigens have employed HLA-A2-restricted TCRs, limiting this approach to those patients expressing this allele. For these patients, TCR gene therapy trials have resulted in both tantalizing successes and lethal adverse events, underscoring the need for careful selection of antigenic targets. Broad and safe application of public antigen-targeted TCR gene therapies will require (i) selecting public antigens that are highly tumor-specific and (ii) targeting multiple epitopes derived from these antigens by obtaining an assortment of TCRs restricted by multiple common MHC alleles. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we pilot an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2.
URI: http://ahro.austin.org.au/austinjspui/handle/1/20141
DOI: 10.1073/pnas.1810653115
ORCID: 0000-0002-3898-950X
PubMed URL: 30348802
Type: Journal Article
Subjects: MHC
NY-ESO-1
T cell receptor gene therapy
TCR
immunotherapy
Appears in Collections:Journal articles

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