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Ex vivo activation of CD56(+) immune cells that eradicate neuroblastoma.
- Source :
-
Cancer research [Cancer Res] 2013 Apr 15; Vol. 73 (8), pp. 2608-18. Date of Electronic Publication: 2013 Feb 25. - Publication Year :
- 2013
-
Abstract
- Despite the use of intensive contemporary multimodal therapy, the overall survival of patients with high-risk neuroblastoma is still less than 50%. Therefore, immunotherapy without cross-resistance and overlapping toxicity has been proposed. In this study, we report the development of a novel strategy to specifically activate and expand human CD56(+) (NCAM1) natural killer (NK) immune cells from normal donors and patients with neuroblastoma. Enriched CD56(+) cells from peripheral blood were mixed with CD56(-) fraction at 1:1 ratio and cultured in the presence of OKT3, interleukin (IL)-2, and -15 for five days and then without OKT3 for 16 more days. The final products contained more than 90% CD56(+) cells and could kill neuroblastoma cells effectively that were originally highly resistant to nonprocessed NK cells. Mechanistically, cytolysis of neuroblastoma was mediated through natural cytotoxicity receptor (NCR), DNAX accessory molecule-1 (DNAM-1; CD226), perforin, and granzyme B. Successful clinical scale-up in a good manufacturing practices (GMP)-compliant bioreactor yielded effector cells that in a neuroblastoma xenograft model slowed tumor growth and extended survival without GVHD. Investigation of CD56(+) cells from patients with neuroblastoma revealed a similar postactivation phenotype and lytic activity. Our findings establish a novel and clinically expedient strategy to generate allogeneic or autologous CD56(+) cells that are highly cytotoxic against neuroblastoma with minimal risk of GVHD.<br /> (©2013 AACR.)
- Subjects :
- Animals
Antigens, Differentiation, T-Lymphocyte immunology
Antigens, Differentiation, T-Lymphocyte metabolism
Cell Culture Techniques standards
Cell Degranulation immunology
Cell Line, Tumor
Coculture Techniques
Cytotoxicity, Immunologic
Disease Models, Animal
Graft vs Host Reaction immunology
Humans
Killer Cells, Natural cytology
Leukocytes, Mononuclear cytology
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
Mice
Natural Killer T-Cells cytology
Natural Killer T-Cells immunology
Natural Killer T-Cells metabolism
Neuroblastoma therapy
Receptors, Natural Killer Cell immunology
Receptors, Natural Killer Cell metabolism
CD56 Antigen metabolism
Killer Cells, Natural immunology
Killer Cells, Natural metabolism
Lymphocyte Activation immunology
Neuroblastoma immunology
Neuroblastoma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 73
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 23440424
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-12-3322