Development of a clinical model for ex vivo expansion of multiple populations of effector cells for adoptive cellular therapy

Cytotherapy
K R MeehanCharles L Sentman

Abstract

We have previously demonstrated a laboratory model for expanding autologous mononuclear cells into populations of effector killer cells. The goal of the current experiments was to develop a good manufacturing practice (GMP) method for expanding clinical-grade activated effector cells that mediate tumor cell killing through various mechanisms that could be infused into patients following high-dose chemotherapy and autologous stem cell transplant. Mobilized mononuclear cells (MNC) from myeloma patients were placed in culture with serum-free AIM V media, interleukin-2 (1000 IU/mL) and OKT-3 (500 ng/mL) at 37 degrees C and 5% CO2. After 7 days of expansion, the cells were analyzed for cell concentration, viability, phenotype and cytotoxicity directed against human myeloma cell lines. Expansion was compared using culture bags and flasks. Cryopreserved expanded cells were also analyzed. This clinical model of ex vivo expansion yielded polyclonal populations of cytotoxic lymphocytes, including CD3+ CD4+ T cells, CD3+ CD8+ T cells, CD8+ CD56+ T cells and CD56+ natural killer cells. Compared with flasks, culture bags provided a 2-3-fold effector cell expansion with minimal risk of contamination. The optimal cell concentration at the tim...Continue Reading

References

Dec 14, 1999·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·M Ito, J A Shizuru
May 9, 2003·The New England Journal of Medicine·J Anthony ChildUNKNOWN Medical Research Council Adult Leukaemia Working Party

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Citations

Sep 20, 2012·Cancer Biotherapy & Radiopharmaceuticals·Wang-Xiong HuHong-Zhi Li
Jul 31, 2010·Journal of Oncology·Claudia PapewalisMatthias Schott
Sep 17, 2011·Pathology·L Bik ToIan D Lewis
Sep 15, 2012·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Kenneth R MeehanMarc S Ernstoff
Oct 5, 2010·Hematology/oncology and Stem Cell Therapy·Garnet Suck, Mickey Boon Chai Koh
May 5, 2009·The Korean journal of laboratory medicine·Duck Cho, Dario Campana

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