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

  • Author(s): Shah, Nina;
  • Martin-Antonio, Beatriz;
  • Yang, Hong;
  • Ku, Stephanie;
  • Lee, Dean A;
  • Cooper, Laurence JN;
  • 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
  • et al.
Abstract

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.

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