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 G Sanger, Diana Pickering, Joanne Kurtzberg, Mitchell S. Cairo

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 1 2006

Fingerprint

Cell Engineering
Lymphokines
Fetal Blood
Lymphocytes
Adoptive Immunotherapy
Transplantation
Serum-Free Culture Media
Blood Cells
Cytokines
Lymphokine-Activated Killer Cells
Interleukin-7
Immunophenotyping
Inbred NOD Mouse
SCID Mice
K562 Cells
Antibodies
Lymphocyte Subsets
Interleukin-12
Interleukin-2
Monocytes

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering. / Ayello, Janet; van de Ven, Carmella; Fortino, Weiwei; Wade-Harris, Cheryl; Satwani, Prakash; Baxi, Laxmi; Simpson, Lynn L.; Sanger, Warren G; Pickering, Diana; Kurtzberg, Joanne; Cairo, Mitchell S.

In: Biology of Blood and Marrow Transplantation, Vol. 12, No. 6, 01.06.2006, p. 608-622.

Research output: Contribution to journalArticle

Ayello, J, van de Ven, C, Fortino, W, Wade-Harris, C, Satwani, P, Baxi, L, Simpson, LL, Sanger, WG, Pickering, D, Kurtzberg, J & Cairo, MS 2006, 'Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering', Biology of Blood and Marrow Transplantation, vol. 12, no. 6, pp. 608-622. https://doi.org/10.1016/j.bbmt.2006.01.009
Ayello, Janet ; van de Ven, Carmella ; Fortino, Weiwei ; Wade-Harris, Cheryl ; Satwani, Prakash ; Baxi, Laxmi ; Simpson, Lynn L. ; Sanger, Warren G ; Pickering, Diana ; Kurtzberg, Joanne ; Cairo, Mitchell S. / Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering. In: Biology of Blood and Marrow Transplantation. 2006 ; Vol. 12, No. 6. pp. 608-622.
@article{a78d676239fc4474b0280350f7b4b70f,
title = "Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering",
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.",
keywords = "Cord blood, Ex vivo, Lymphokine-activated killer, Natural killer, Natural killer receptor",
author = "Janet Ayello and {van de Ven}, Carmella and Weiwei Fortino and Cheryl Wade-Harris and Prakash Satwani and Laxmi Baxi and Simpson, {Lynn L.} and Sanger, {Warren G} and Diana Pickering and Joanne Kurtzberg and Cairo, {Mitchell S.}",
year = "2006",
month = "6",
day = "1",
doi = "10.1016/j.bbmt.2006.01.009",
language = "English (US)",
volume = "12",
pages = "608--622",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering

AU - Ayello, Janet

AU - van de Ven, Carmella

AU - Fortino, Weiwei

AU - Wade-Harris, Cheryl

AU - Satwani, Prakash

AU - Baxi, Laxmi

AU - Simpson, Lynn L.

AU - Sanger, Warren G

AU - Pickering, Diana

AU - Kurtzberg, Joanne

AU - Cairo, Mitchell S.

PY - 2006/6/1

Y1 - 2006/6/1

N2 - 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.

AB - 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.

KW - Cord blood

KW - Ex vivo

KW - Lymphokine-activated killer

KW - Natural killer

KW - Natural killer receptor

UR - http://www.scopus.com/inward/record.url?scp=33646811846&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646811846&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2006.01.009

DO - 10.1016/j.bbmt.2006.01.009

M3 - Article

VL - 12

SP - 608

EP - 622

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 6

ER -