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Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells. | LitMetric

Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells.

J Immunother Cancer

Clinical Research Division, D3-100 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave, Seattle, WA 98109 USA ; Department of Medicine, University of Washington, Seattle, WA USA ; Department of Melanoma Medical Oncology, UT MD Anderson Cancer Center, 7455 Fannin St, Unit 904, Houston, TX 77054 USA.

Published: October 2014

AI Article Synopsis

  • The study explores a new method for generating specific T cells to treat cancer, focusing on NY-ESO-1 positive sarcomas, through the combination of IL-21 modulation and tetramer-guided cell sorting.
  • In clinical trials with 6 patients, the technique successfully enriched NY-ESO-1 specific T cells from a low initial frequency to over 90% and produced large quantities of effective cells with memory characteristics.
  • This innovative approach lays the groundwork for expanding adoptive T cell therapy by targeting additional tumor antigens, potentially making it a more versatile and effective cancer treatment.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196009PMC
http://dx.doi.org/10.1186/s40425-014-0036-yDOI Listing

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