Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering

Janet Ayello, Carmella van de Ven, Weiwei Fortino, Cheryl Wade-Harris, Prakash Satwani, Laxmi Baxi, Lynn L. Simpson, Warren Sanger, Diana Pickering, Joanne Kurtzberg, Mitchell S. Cairo

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Cord blood (CB) natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic cells are poorly characterized but might be used to treat minimal residual and/or recurrent malignant disease. Currently, there is no mechanism to use CB for adoptive cancer cellular immunotherapy after CB transplantation (CBT). Recognizing this as a deficiency, we hypothesized that CB aliquots could be engineered ex vivo for potential donor lymphocyte infusion after CBT. Cryopreserved CB aliquots were thawed, depleted of monocytes, and cultured in serum-free medium alone or serum-free medium with anti-CD3 and interleukins 2, 7, and 12 combined with antibody/cytokines for 48 hours. Immunophenotyping, cytotoxicity, and proliferation were evaluated. A significant expansion of CD3+ was seen, in addition to increases in lymphocyte subsets of CD8+, CD8+/CD25+, and CD3+/45RO+ versus medium alone. A significant enhancement of CD3 proliferation (P < .001), NK cytotoxicity, NK subset expansion, LAK cytotoxicity, and T-helper 1 subset expansion was also demonstrated. Significant enrichment was seen in NK CD16+/CD56+bright, CD16+/CD56+dim, CD56+bright and CD56+dim/KIR3DL1+, CD56+bright and CD56+dim/KIR2DL1+, CD56+bright and CD56+dim/KIR2DL2+ and CD94+/NKG2a+ subsets. These increases in CB NK subsets were in part secondary to augmentation of cell survival. Further, survival of NOD-SCID mice xenografted with human K562 cells and treated with CB cells expanded with antibody/cytokines was significantly higher than that in animals that received no treatment (phosphate buffered saline) and those that were treated with CB ex vivo expanded in medium alone (P < .005, respectively). These data suggest that cryopreserved CB cells could be ex vivo engineered for potential use as adoptive cancer cellular immunotherapy for donor lymphocyte infusion after CBT.

Original languageEnglish (US)
Pages (from-to)608-622
Number of pages15
JournalBiology of Blood and Marrow Transplantation
Volume12
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • Cord blood
  • Ex vivo
  • Lymphokine-activated killer
  • Natural killer
  • Natural killer receptor

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Ayello, J., van de Ven, C., Fortino, W., Wade-Harris, C., Satwani, P., Baxi, L., Simpson, L. L., Sanger, W., Pickering, D., Kurtzberg, J., & Cairo, M. S. (2006). Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering. Biology of Blood and Marrow Transplantation, 12(6), 608-622. https://doi.org/10.1016/j.bbmt.2006.01.009