Details

Autor(en) / Beteiligte

• Shah, Nina
• Martin-Antonio, Beatriz
• Yang, Hong
• Ku, Stephanie
• Lee, Dean A
• Cooper, Laurence J N
• Decker, William K
• Li, Sufang
• Robinson, Simon N
• Sekine, Takuya
• Parmar, Simrit
• Gribben, John
• Wang, Michael
• Rezvani, Katy
• Yvon, Eric
• Najjar, Amer
• Burks, Jared
• Kaur, Indreshpal
• Champlin, Richard E
• Bollard, Catherine M
• Shpall, Elizabeth J
• Alici, Evren

Titel

Antigen presenting cell-mediated expansion of human umbilical cord blood yields log-scale expansion of natural killer cells with anti-myeloma activity

Ist Teil von

• PloS one, 2013-10, Vol.8 (10), p.e76781-e76781

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2013

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• Natural killer (NK) cells are important mediators of anti-tumor immunity and are active against several hematologic malignancies, including multiple myeloma (MM). Umbilical cord blood (CB) is a promising source of allogeneic NK cells but large scale ex vivo expansion is required for generation of clinically relevant CB-derived NK (CB-NK) cell doses. Here we describe a novel strategy for expanding NK cells from cryopreserved CB units using artificial antigen presenting feeder cells (aAPC) in a gas permeable culture system. After 14 days, mean fold expansion of CB-NK cells was 1848-fold from fresh and 2389-fold from cryopreserved CB with >95% purity for NK cells (CD56(+)/CD3(-)) and less than 1% CD3(+) cells. Though surface expression of some cytotoxicity receptors was decreased, aAPC-expanded CB-NK cells exhibited a phenotype similar to CB-NK cells expanded with IL-2 alone with respect to various inhibitory receptors, NKG2C and CD94 and maintained strong expression of transcription factors Eomesodermin and T-bet. Furthermore, CB-NK cells formed functional immune synapses with and demonstrated cytotoxicity against various MM targets. Finally, aAPC-expanded CB-NK cells showed significant in vivo activity against MM in a xenogenic mouse model. Our findings introduce a clinically applicable strategy for the generation of highly functional CB-NK cells which can be used to eradicate MM.