Characterization and ex vivo expansion of human placenta-derived natural killer cells for cancer immunotherapy

Lin Kang, Vanessa Voskinarian-Berse, Eric Law, Tiffany Reddin, Mohit Bhatia, Alexandra Hariri, Yuhong Ning, David Dong, Timothy Maguire, Martin Yarmush, Wolfgang Hofgartner, Stewart Abbot, Xiaokui Zhang, Robert Hariri

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Recent clinical studies suggest that adoptive transfer of donor-derived natural killer (NK) cells may improve clinical outcome in hematological malignancies and some solid tumors by direct anti-tumor effects as well as by reduction of graft versus host disease (GVHD). NK cells have also been shown to enhance transplant engraftment during allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. The limited ex vivo expansion potential of NK cells from peripheral blood (PB) or umbilical cord blood (UCB) has however restricted their therapeutic potential. Here we define methods to efficiently generate NK cells from donor-matched, full-term human placenta perfusate (termed Human Placenta-Derived Stem Cell, HPDSC) and UCB. Following isolation from cryopreserved donor-matched HPDSC and UCB units, CD56+CD3-placenta-derived NK cells, termed pNK cells, were expanded in culture for up to 3 weeks to yield an average of 1.2 billion cells per donor that were >80% CD56+CD3-, comparable to doses previously utilized in clinical applications. Ex vivo-expanded pNK cells exhibited a marked increase in anti-tumor cytolytic activity coinciding with the significantly increased expression of NKG2D, NKp46, and NKp44 (p < 0.001, p < 0.001, and p < 0.05, respectively). Strong cytolytic activity was observed against a wide range of tumor cell lines in vitro. pNK cells display a distinct microRNA (miRNA) expression profile, immunophenotype, and greater anti-tumor capacity in vitro compared to PB NK cells used in recent clinical trials. With further development, pNK may represent a novel and effective cellular immunotherapy for patients with high clinical needs and few other therapeutic options.

Original languageEnglish (US)
Article numberArticle 101
JournalFrontiers in immunology
Volume4
Issue numberMAY
DOIs
StatePublished - Sep 17 2013

Fingerprint

Natural Killer Cells
Immunotherapy
Placenta
Fetal Blood
Neoplasms
Tissue Donors
Hematologic Neoplasms
Stem Cells
Adoptive Transfer
Hematopoietic Stem Cell Transplantation
Graft vs Host Disease
Tumor Cell Line
MicroRNAs
Blood Cells
Clinical Trials
Transplants
Therapeutics
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

  • Anti-tumor cytolytic activity
  • Cellular immunotherapy
  • Ex vivo expansion
  • MiRNA
  • Placental-derived natural killer cells

Cite this

Kang, L., Voskinarian-Berse, V., Law, E., Reddin, T., Bhatia, M., Hariri, A., ... Hariri, R. (2013). Characterization and ex vivo expansion of human placenta-derived natural killer cells for cancer immunotherapy. Frontiers in immunology, 4(MAY), [Article 101]. https://doi.org/10.3389/fimmu.2013.00101
Kang, Lin ; Voskinarian-Berse, Vanessa ; Law, Eric ; Reddin, Tiffany ; Bhatia, Mohit ; Hariri, Alexandra ; Ning, Yuhong ; Dong, David ; Maguire, Timothy ; Yarmush, Martin ; Hofgartner, Wolfgang ; Abbot, Stewart ; Zhang, Xiaokui ; Hariri, Robert. / Characterization and ex vivo expansion of human placenta-derived natural killer cells for cancer immunotherapy. In: Frontiers in immunology. 2013 ; Vol. 4, No. MAY.
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Kang, L, Voskinarian-Berse, V, Law, E, Reddin, T, Bhatia, M, Hariri, A, Ning, Y, Dong, D, Maguire, T, Yarmush, M, Hofgartner, W, Abbot, S, Zhang, X & Hariri, R 2013, 'Characterization and ex vivo expansion of human placenta-derived natural killer cells for cancer immunotherapy', Frontiers in immunology, vol. 4, no. MAY, Article 101. https://doi.org/10.3389/fimmu.2013.00101

Characterization and ex vivo expansion of human placenta-derived natural killer cells for cancer immunotherapy. / Kang, Lin; Voskinarian-Berse, Vanessa; Law, Eric; Reddin, Tiffany; Bhatia, Mohit; Hariri, Alexandra; Ning, Yuhong; Dong, David; Maguire, Timothy; Yarmush, Martin; Hofgartner, Wolfgang; Abbot, Stewart; Zhang, Xiaokui; Hariri, Robert.

In: Frontiers in immunology, Vol. 4, No. MAY, Article 101, 17.09.2013.

Research output: Contribution to journalArticle

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T1 - Characterization and ex vivo expansion of human placenta-derived natural killer cells for cancer immunotherapy

AU - Kang, Lin

AU - Voskinarian-Berse, Vanessa

AU - Law, Eric

AU - Reddin, Tiffany

AU - Bhatia, Mohit

AU - Hariri, Alexandra

AU - Ning, Yuhong

AU - Dong, David

AU - Maguire, Timothy

AU - Yarmush, Martin

AU - Hofgartner, Wolfgang

AU - Abbot, Stewart

AU - Zhang, Xiaokui

AU - Hariri, Robert

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