Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8+ T cells. Issue 1 (14th October 2014)

• Record Type: Journal Article
• Authors: Pollack, Seth M; Jones, Robin L; Farrar, Erik A; Lai, Ivy P; Lee, Sylvia M; Cao, Jianhong; Pillarisetty, Venu G; Hoch, Benjamin L; Gullett, Ashley; Bleakley, Marie; Conrad, Ernest U; Eary, Janet F; Shibuya, Kendall C; Warren, Edus H; Carstens, Jason N; Heimfeld, Shelly; Riddell, Stanley R; Yee, Cassian
• Is Part Of: Journal for immunotherapy of cancer. Volume 2:Issue 1(2013)
• Publication Date: 2014-10-14
• Subjects: Adoptive T cell therapy -- NY-ESO-1 -- Synovial sarcoma -- Myxoid -- Liposarcoma -- Immunotherapy -- Antigen specific T cells -- Tetramer -- Influx cell sorting; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-014-0036-y
• Languages: English
• ISSNs: 2051-1426

Abstract

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.