Author:
Somerville Robert PT,Devillier Laura,Parkhurst Maria R,Rosenberg Steven A,Dudley Mark E
Abstract
Abstract
Background
To simplify clinical scale lymphocyte expansions, we investigated the use of the WAVE®, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes.
Methods
We have developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant numbers of cells for our adoptive cell transfer clinical protocols.
Results
TIL and genetically modified PBL were rapidly expanded to clinically relevant scales in both static bags and the WAVE bioreactor. Both bioreactors produced comparable numbers of cells; however the cultures generated in the WAVE bioreactor had a higher percentage of CD4+ cells and had a less activated phenotype.
Conclusions
The WAVE bioreactor simplifies the process of rapidly expanding tumor reactive lymphocytes under GMP conditions, and provides an alternate approach to cell generation for ACT protocols.
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference34 articles.
1. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR: Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009, 27: 6199-6206. 10.1200/JCO.2009.23.4799.
2. Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S: Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000, 18: 158-166.
3. Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K: High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999, 17: 2105-2116.
4. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010, 363: 711-723. 10.1056/NEJMoa1003466.
5. Atkins MB, Kunkel L, Sznol M, Rosenberg SA: High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000, 6 (Suppl 1): S11-S14.
Cited by
82 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献