Immunomodulation of early engrafted natural killer cells with interleukin-2 and interferon-α in autologous stem cell transplantation

L. F. Porrata, D. J. Inwards, Martha Lacy, Svetomir Nenad Markovic

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

High relapse rates during the first year after autologous stem cell transplantation (ASCT) for multiple myeloma or non-Hodgkin lymphoma are due to the failure of high-dose chemotherapy to eradicate minimal residual disease. Post-ASCT immunorecovery studies have shown that quantities of natural killer (NK) cells return to normal within 1 month post-ASCT in contrast to the recovery of T and B cell populations (up to 1 year). Pre-clinical studies have demonstrated that NK cells have potent antitumor activity. IL-2 and IFN-α enhance NK-cell activity. We investigated the efficacy of IL-2 and IFN-α to up-regulate NK-cell cytotoxicity at 14 days post ASCT. Twenty patients undergoing ASCT had PBMCs collected pretransplantation and at 14 days post transplantation. PBMCs (effector cells) from each blood sample were incubated in vitro with IFN-α and IL-2 at 10 000 IU/ml. NK cell activity was determined by sodium chromate 51Cr release assay for lysis of K562 target cells. IL-2 and IFN-α each increased lysis of K562 cells compared with placebo (effector-to-target ratio, 50:1, P < 0.001). Increased NK cell activity occurred in samples from all patients. IL-2 and IFN-α up-regulated NK cell activity at 14 days post ASCT. They may be useful as immunomodulators as early as 14 days post ASCT to eradicate or control minimal residual disease.

Original languageEnglish (US)
Pages (from-to)673-680
Number of pages8
JournalBone Marrow Transplantation
Volume28
Issue number7
DOIs
StatePublished - 2001

Fingerprint

Immunomodulation
Stem Cell Transplantation
Natural Killer Cells
Interferons
Interleukin-2
K562 Cells
Residual Neoplasm
Immunologic Factors
Multiple Myeloma
Non-Hodgkin's Lymphoma
Blood Cells
B-Lymphocytes
Up-Regulation
Transplantation
Placebos
T-Lymphocytes
Recurrence
Drug Therapy
Population

Keywords

  • Interferon-alpha
  • Interleukin-2
  • Natural killer cells
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{04b7c9aebd85463cbfadfde56225a156,
title = "Immunomodulation of early engrafted natural killer cells with interleukin-2 and interferon-α in autologous stem cell transplantation",
abstract = "High relapse rates during the first year after autologous stem cell transplantation (ASCT) for multiple myeloma or non-Hodgkin lymphoma are due to the failure of high-dose chemotherapy to eradicate minimal residual disease. Post-ASCT immunorecovery studies have shown that quantities of natural killer (NK) cells return to normal within 1 month post-ASCT in contrast to the recovery of T and B cell populations (up to 1 year). Pre-clinical studies have demonstrated that NK cells have potent antitumor activity. IL-2 and IFN-α enhance NK-cell activity. We investigated the efficacy of IL-2 and IFN-α to up-regulate NK-cell cytotoxicity at 14 days post ASCT. Twenty patients undergoing ASCT had PBMCs collected pretransplantation and at 14 days post transplantation. PBMCs (effector cells) from each blood sample were incubated in vitro with IFN-α and IL-2 at 10 000 IU/ml. NK cell activity was determined by sodium chromate 51Cr release assay for lysis of K562 target cells. IL-2 and IFN-α each increased lysis of K562 cells compared with placebo (effector-to-target ratio, 50:1, P < 0.001). Increased NK cell activity occurred in samples from all patients. IL-2 and IFN-α up-regulated NK cell activity at 14 days post ASCT. They may be useful as immunomodulators as early as 14 days post ASCT to eradicate or control minimal residual disease.",
keywords = "Interferon-alpha, Interleukin-2, Natural killer cells, Stem cell transplantation",
author = "Porrata, {L. F.} and Inwards, {D. J.} and Martha Lacy and Markovic, {Svetomir Nenad}",
year = "2001",
doi = "10.1038/sj.bmt.1703203",
language = "English (US)",
volume = "28",
pages = "673--680",
journal = "Bone Marrow Transplantation",
issn = "0268-3369",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Immunomodulation of early engrafted natural killer cells with interleukin-2 and interferon-α in autologous stem cell transplantation

AU - Porrata, L. F.

AU - Inwards, D. J.

AU - Lacy, Martha

AU - Markovic, Svetomir Nenad

PY - 2001

Y1 - 2001

N2 - High relapse rates during the first year after autologous stem cell transplantation (ASCT) for multiple myeloma or non-Hodgkin lymphoma are due to the failure of high-dose chemotherapy to eradicate minimal residual disease. Post-ASCT immunorecovery studies have shown that quantities of natural killer (NK) cells return to normal within 1 month post-ASCT in contrast to the recovery of T and B cell populations (up to 1 year). Pre-clinical studies have demonstrated that NK cells have potent antitumor activity. IL-2 and IFN-α enhance NK-cell activity. We investigated the efficacy of IL-2 and IFN-α to up-regulate NK-cell cytotoxicity at 14 days post ASCT. Twenty patients undergoing ASCT had PBMCs collected pretransplantation and at 14 days post transplantation. PBMCs (effector cells) from each blood sample were incubated in vitro with IFN-α and IL-2 at 10 000 IU/ml. NK cell activity was determined by sodium chromate 51Cr release assay for lysis of K562 target cells. IL-2 and IFN-α each increased lysis of K562 cells compared with placebo (effector-to-target ratio, 50:1, P < 0.001). Increased NK cell activity occurred in samples from all patients. IL-2 and IFN-α up-regulated NK cell activity at 14 days post ASCT. They may be useful as immunomodulators as early as 14 days post ASCT to eradicate or control minimal residual disease.

AB - High relapse rates during the first year after autologous stem cell transplantation (ASCT) for multiple myeloma or non-Hodgkin lymphoma are due to the failure of high-dose chemotherapy to eradicate minimal residual disease. Post-ASCT immunorecovery studies have shown that quantities of natural killer (NK) cells return to normal within 1 month post-ASCT in contrast to the recovery of T and B cell populations (up to 1 year). Pre-clinical studies have demonstrated that NK cells have potent antitumor activity. IL-2 and IFN-α enhance NK-cell activity. We investigated the efficacy of IL-2 and IFN-α to up-regulate NK-cell cytotoxicity at 14 days post ASCT. Twenty patients undergoing ASCT had PBMCs collected pretransplantation and at 14 days post transplantation. PBMCs (effector cells) from each blood sample were incubated in vitro with IFN-α and IL-2 at 10 000 IU/ml. NK cell activity was determined by sodium chromate 51Cr release assay for lysis of K562 target cells. IL-2 and IFN-α each increased lysis of K562 cells compared with placebo (effector-to-target ratio, 50:1, P < 0.001). Increased NK cell activity occurred in samples from all patients. IL-2 and IFN-α up-regulated NK cell activity at 14 days post ASCT. They may be useful as immunomodulators as early as 14 days post ASCT to eradicate or control minimal residual disease.

KW - Interferon-alpha

KW - Interleukin-2

KW - Natural killer cells

KW - Stem cell transplantation

UR - http://www.scopus.com/inward/record.url?scp=0034750613&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034750613&partnerID=8YFLogxK

U2 - 10.1038/sj.bmt.1703203

DO - 10.1038/sj.bmt.1703203

M3 - Article

C2 - 11704790

AN - SCOPUS:0034750613

VL - 28

SP - 673

EP - 680

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

SN - 0268-3369

IS - 7

ER -