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Isolation and characterization of NY-ESO-1-specific T cell receptors restricted on various MHC molecules.

A new interesting article has been published in Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10702-E10711. doi: 10.1073/pnas.1810653115. Epub 2018 Oct 22. and titled:

Isolation and characterization of NY-ESO-1-specific T cell receptors restricted on various MHC molecules.

Authors of this article are:

Bethune MT, Li XH, Yu J, McLaughlin J, Cheng D, Mathis C, Moreno BH, Woods K,, Knights AJ, Garcia-Diaz A, Wong S, Hu-Lieskovan S, Puig-Saus C, Cebon J,, Ribas A,,0, Yang L,,0, Witte ON,, Baltimore D.

A summary of the article is shown below:

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.

Check out the article’s website on Pubmed for more information:

This article is a good source of information and a good way to become familiar with topics such as:

MHC;NY-ESO-1;T cell receptor gene therapy;TCR;immunotherapy


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