OBJECTIVE: Cord blood (CB) is limited by the absence of available donor effector cells for post-unrelated CB transplantation adoptive cellular immunotherapy. We reported the ability to ex vivo expand (EvE) CB mononuclear cells (MNC) after short-term incubation with anti-CD3, interleukin (IL)-2, IL-7, and IL-12 (antibody/cytokine [AB/CY]) into subpopulations of CD3(-)/56(+) natural killer (NK) cells with enhanced in vitro and in vivo tumor cytotoxicity. MATERIALS AND METHODS: We compared 2- vs 7-day EvE of rethawed CB MNCs in AB/CY and activation of NK and NK-like T (NKT) cell (CD3(+)/56(+)) subsets expressing specific NK-cell receptors along with IL-15, IL-18, and interferon-gamma production. RESULTS: Nonadherent 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 natural cytoxicity receptor CD94/NKG2A were decreased (p<0.001), while those expressing activating natural cytoxicity receptor CD94/NKG2D receptor and activating NK and NKT KIR2DS4 subsets were significantly increased (p<0.001). IL-18 and interferon-gamma protein production was also significantly increased (p<0.001 and p<0.05, respectively). Lysosomal-associated membrane protein-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 that appear to be cytolytic based on the cell repertoire and could be utilized in the future as adoptive cellular immunotherapy post-unrelated CB transplantation.
OBJECTIVE: Cord blood (CB) is limited by the absence of available donor effector cells for post-unrelated CB transplantation adoptive cellular immunotherapy. We reported the ability to ex vivo expand (EvE) CB mononuclear cells (MNC) after short-term incubation with anti-CD3, interleukin (IL)-2, IL-7, and IL-12 (antibody/cytokine [AB/CY]) into subpopulations of CD3(-)/56(+) natural killer (NK) cells with enhanced in vitro and in vivo tumorcytotoxicity. MATERIALS AND METHODS: We compared 2- vs 7-day EvE of rethawed CB MNCs in AB/CY and activation of NK and NK-like T (NKT) cell (CD3(+)/56(+)) subsets expressing specific NK-cell receptors along with IL-15, IL-18, and interferon-gamma production. RESULTS: Nonadherent 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 natural cytoxicity receptor CD94/NKG2A were decreased (p<0.001), while those expressing activating natural cytoxicity receptor CD94/NKG2D receptor and activating NK and NKT KIR2DS4 subsets were significantly increased (p<0.001). IL-18 and interferon-gamma protein production was also significantly increased (p<0.001 and p<0.05, respectively). Lysosomal-associated membrane protein-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 tumorcytotoxicity 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 that appear to be cytolytic based on the cell repertoire and could be utilized in the future as adoptive cellular immunotherapy post-unrelated CB transplantation.
Authors: Sumithira Vasu; Maria Berg; Jan Davidson-Moncada; Xin Tian; Herb Cullis; Richard W Childs Journal: Cytotherapy Date: 2015-11 Impact factor: 5.414
Authors: Yaya Chu; Sanghoon Lee; Tishi Shah; Changhong Yin; Matthew Barth; Rodney R Miles; Janet Ayello; Erin Morris; Lauren Harrison; Carmella Van de Ven; Paul Galardy; Stanton C Goldman; Megan S Lim; Michelle Hermiston; Linda M McAllister-Lucas; Lisa Giulino-Roth; Sherrie L Perkins; Mitchell S Cairo Journal: Oncoimmunology Date: 2018-10-11 Impact factor: 8.110
Authors: Stacey L Berg; Mitchell S Cairo; Heidi Russell; Janet Ayello; Ashish Mark Ingle; Henry Lau; Nianhang Chen; Peter C Adamson; Susan M Blaney Journal: J Clin Oncol Date: 2010-12-13 Impact factor: 44.544
Authors: Mark B Geyer; Judith S Jacobson; Jason Freedman; Diane George; Virginia Moore; Carmella van de Ven; Prakash Satwani; Monica Bhatia; James H Garvin; Mary Brigid Bradley; Lauren Harrison; Erin Morris; Phyllis Della-Latta; Joseph Schwartz; Lee A Baxter-Lowe; Mitchell S Cairo Journal: Br J Haematol Date: 2011-08-16 Impact factor: 6.998