Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8+ T cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Seth M Pollack, Robin L Jones, Erik A Farrar, Ivy P Lai, Sylvia M Lee, Jianhong Cao, Venu G Pillarisetty, Benjamin L Hoch, Ashley Gullett, Marie Bleakley, Ernest U Conrad, Janet F Eary, Kendall C Shibuya, Edus H Warren, Jason N Carstens, Shelly Heimfeld, Stanley R Riddell, Cassian Yee

ABSTRACT

BACKGROUND: Adoptive T cell therapy represents an attractive modality for the treatment of patients with cancer. Peripheral blood mononuclear cells have been used as a source of antigen specific T cells but the very low frequency of T cells recognizing commonly expressed antigens such as NY-ESO-1 limit the applicability of this approach to other solid tumors. To overcome this, we tested a strategy combining IL-21 modulation during in vitro stimulation with first-in-class use of tetramer-guided cell sorting to generate NY-ESO-1 specific cytotoxic T lymphocytes (CTL). METHODS: CTL generation was evaluated in 6 patients with NY-ESO-1 positive sarcomas, under clinical manufacturing conditions and characterized for phenotypic and functional properties. RESULTS: Following in vitro stimulation, T cells stained with NY-ESO-1 tetramer were enriched from frequencies as low as 0.4% to >90% after single pass through a clinical grade sorter. NY-ESO-1 specific T cells were generated from all 6 patients. The final products expanded on average 1200-fold to a total of 36 billion cells, were oligoclonal and contained 67-97% CD8(+), tetramer(+) T cells with a memory phenotype that recognized endogenous NY-ESO-1. CONCLUSION: This study represents the first series using tetramer-guided cell sorting to generate T cells for adoptive therapy. This approach, when used to target more broadly expressed tumor antigens such as WT-1 and additional Cancer-Testis antigens will enhance the scope and feasibility of adoptive T cell therapy. More... »

PAGES

36

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40425-014-0036-y

DOI

http://dx.doi.org/10.1186/s40425-014-0036-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022863025

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25317334


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