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Pollack SM, Jones RL, Farrar EA, et al. Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells. J Immunother Cancer. 2014;2(1):36doi: 10.1186/s40425-014-0036-y.
Pollack, S. M., Jones, R. L., Farrar, E. A., Lai, I. P., Lee, S. M., Cao, J., Pillarisetty, V. G., Hoch, B. L., Gullett, A., Bleakley, M., Conrad, E. U., Eary, J. F., Shibuya, K. C., Warren, E. H., Carstens, J. N., Heimfeld, S., Riddell, S. R., & Yee, C. (2014). Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells. Journal for immunotherapy of cancer, 2(1), 36. https://doi.org/10.1186/s40425-014-0036-y
Pollack, Seth M, et al. "Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells." Journal for immunotherapy of cancer vol. 2,1 (2014): 36. doi: https://doi.org/10.1186/s40425-014-0036-y
Pollack SM, Jones RL, Farrar EA, Lai IP, Lee SM, Cao J, Pillarisetty VG, Hoch BL, Gullett A, Bleakley M, Conrad EU, Eary JF, Shibuya KC, Warren EH, Carstens JN, Heimfeld S, Riddell SR, Yee C. Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells. J Immunother Cancer. 2014 Oct 14;2(1):36. doi: 10.1186/s40425-014-0036-y. eCollection 2014. PMID: 25317334; PMCID: PMC4196009.
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J Immunother Cancer. 2014 Oct 14;2(1):36. doi: 10.1186/s40425-014-0036-y. eCollection 2014.

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

Journal for immunotherapy of cancer

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

Affiliations

  1. 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.
  2. Clinical Research Division, D3-100 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave, Seattle, WA 98109 USA.
  3. Clinical Research Division, D3-100 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave, Seattle, WA 98109 USA ; Institute for Advanced Study, Technical University of Munich, Munich, Germany.
  4. Clinical Research Division, D3-100 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave, Seattle, WA 98109 USA ; Department of Surgery, University of Washington, Seattle, WA USA.
  5. Department of Pathology, University of Washington, Seattle, WA USA.
  6. Clinical Research Division, D3-100 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave, Seattle, WA 98109 USA ; Department of Pediatrics, University of Washington, Seattle, WA USA.
  7. Department of Orthopedics, University of Washington, Seattle, WA USA.
  8. Department of Radiology, University of Alabama, Birmingham, AL USA.
  9. 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 ; Institute for Advanced Study, Technical University of Munich, Munich, Germany.
  10. 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.

PMID: 25317334 PMCID: PMC4196009 DOI: 10.1186/s40425-014-0036-y

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.

Keywords: Adoptive T cell therapy; Antigen specific T cells; Immunotherapy; Influx cell sorting; Liposarcoma; Myxoid; NY-ESO-1; Synovial sarcoma; Tetramer

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