Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8+ T cells
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  • 作者:Seth M Pollack (1) (2)
    Robin L Jones (1) (2)
    Erik A Farrar (1)
    Ivy P Lai (1) (8)
    Sylvia M Lee (1) (2)
    Jianhong Cao (1)
    Venu G Pillarisetty (1) (3)
    Benjamin L Hoch (4)
    Ashley Gullett (4)
    Marie Bleakley (1) (5)
    Ernest U Conrad III (6)
    Janet F Eary (7)
    Kendall C Shibuya (1)
    Edus H Warren (1) (2)
    Jason N Carstens (1)
    Shelly Heimfeld (1)
    Stanley R Riddell (1) (2) (8)
    Cassian Yee (1) (2) (9)

    1. Clinical Research Division
    ; D3-100 Fred Hutchinson Cancer Research Center ; 1100 Fairview Ave ; Seattle ; WA ; 98109 ; USA
    2. Department of Medicine
    ; University of Washington ; Seattle ; WA ; USA
    8. Institute for Advanced Study
    ; Technical University of Munich ; Munich ; Germany
    3. Department of Surgery
    ; University of Washington ; Seattle ; WA ; USA
    4. Department of Pathology
    ; University of Washington ; Seattle ; WA ; USA
    5. Department of Pediatrics
    ; University of Washington ; Seattle ; WA ; USA
    6. Department of Orthopedics
    ; University of Washington ; Seattle ; WA ; USA
    7. Department of Radiology
    ; University of Alabama ; Birmingham ; AL ; USA
    9. Department of Melanoma Medical Oncology
    ; UT MD Anderson Cancer Center ; 7455 Fannin St ; Unit 904 ; Houston ; TX ; 77054 ; USA
  • 关键词:Adoptive T cell therapy ; NY ; ESO ; 1 ; Synovial sarcoma ; Myxoid ; Liposarcoma ; Immunotherapy ; Antigen specific T cells ; Tetramer ; Influx cell sorting
  • 刊名:Journal for Immunotherapy of Cancer
  • 出版年:2014
  • 出版时间:December 2014
  • 年:2014
  • 卷:2
  • 期:1
  • 全文大小:910 KB
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  • 刊物主题:Oncology;
  • 出版者:BioMed Central
  • ISSN:2051-1426
文摘
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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