| Title | Characterization of natural killer (NK) and natural killer-like T (NKT) cells derived from ex-vivo expanded and activated cord blood mononuclear cells: Implications for adoptive cellular immunotherapy (ACI). | | Author(s) | Ayello J, van de Ven C, Cairo E, Hochberg J, Baxi L, Satwani P, Cairo MS | | Institution | Department of Pediatrics, Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University, New York, New York. | | Source | Exp Hematol 2009 Jul 25. | | Abstract | OBJECTIVE: Cord blood (CB) is limited by the absence of available donor effector cells for post unrelated CB transplantation (UCBT) adoptive cellular immunotherapy (ACI). We reported the ability to ex-vivo expand (EvE) CB MNC after short-term incubation with anti-CD3, IL-2, IL-7 and IL-12 (AB/CY) into subpopulations of CD3(-)/56(+) NK cells with enhanced in-vitro and in-vivo tumor cytotoxicity.
METHODS: We compared 2 vs 7 day EvE of rethawed CB MNCs in AB/CY and activation of NK and NKT-like (CD3(+)/56(+)) subsets expressing specific NK cell receptors (NKRs) along with IL-15, IL-18 and IFN-gamma production.
RESULTS: Non-adherent total cell number were significantly increased at day 7 (p<0.001) along with NK cell number (20-fold) and an enrichment in NKT-like subsets (36-fold). There was no change in the NK(dim) subset; yet, the NKT(bright) and NKT KIR3DL1(dim) subsets were significantly increased (p<0.05). NK cells expressing the inhibitory NCR CD94/NKG2A was decreased (p<0.001) while those expressing activating NCR CD94/NKG2D receptor, and activating NK and NKT KIR2DS4 subsets were significantly increased (p<0.001). IL-18 and IFN-gamma protein production was also significantly increased (p<0.001 and p<0.05, respectively). LAMP-1 and granzyme B expression were increased (p<0.001 and p>0.01, respectively) which correlated with the significant increase in NK, LAK and tumor cytotoxicity of the EvE cells.
CONCLUSION: This study demonstrates that previously cryopreserved and rethawed CB MNCs can be EvE up to 7 days to yield viable and activated NK and NKT-like subsets which appear to be cytolytic based on the cell repertoire and could be utilized in the future as ACI post UCBT. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19638292 |
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