Immunological Consequences of Interleukin 12 Administration after Autologous Stem Cell Transplantation

David Pelloso, Katherine Cyran, Lynette Timmons, Brian T. Williams, Michael Robertson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: The purpose is to determine the immunological effects of recombinant human interleukin (rhIL)-12 therapy after autologous stem cell transplantation. Experimental Design: Twelve patients (8 non-Hodgkin's lymphoma, 2 Hodgkin's disease, and 2 plasma cell myeloma) were treated with rhIL-12 by bolus i.v. injection in doses of 30, 100, or 250 ng/kg starting at a median of 66 days post-transplant. Immunological assays were performed using serum and peripheral blood mononuclear cell (PBMC) samples obtained on study. Results: Dose-dependent increases in the total lymphocyte count occurred during rhIL-12 therapy. The absolute number of peripheral blood CD4 T cells increased up to 16.3-fold, CD8 T cells up to 20.5-fold, B cells up to 11-fold, and natural killer (NK) cells up to 12.3-fold during rhIL-12 administration and returned to pretreatment baseline levels after discontinuation of rhIL-12. CD56 bright NK cells expanded dramatically in the blood of a patient with baseline lymphopenia before rhIL-12 therapy. In vitro proliferation of patient PBMCs in response to IL-12 was indistinguishable from that of PBMCs obtained from healthy control subjects. Moreover, spontaneous in vitro proliferation of patient PBMCs increased significantly during rhIL-12 therapy. Increased levels of IFN-γ and IL-18 were detected in the serum of patients treated in the 100 and 250 ng/kg dose cohorts during the first multiple dose cycle. Conclusions: Expansion of T, B, and NK cells occurs in vivo during rhIL-12 therapy after autologous stem cell transplantation for hematological malignancies. In contrast to their striking defect in IL-12-induced IFN-γ production, posttransplant patient PBMCs exhibit normal proliferative responses to IL-12 in vitro. Additional investigation of rhIL-12 for posttransplantation immunotherapy is warranted.

Original languageEnglish
Pages (from-to)1935-1942
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number6
DOIs
StatePublished - Mar 15 2004

Fingerprint

Stem Cell Transplantation
Interleukin-12
Natural Killer Cells
T-Lymphocytes
Therapeutics
Lymphopenia
Natural Killer T-Cells
Interleukin-18
Lymphocyte Count
Hematologic Neoplasms
Serum
Multiple Myeloma
Hodgkin Disease
Non-Hodgkin's Lymphoma
Immunotherapy
Blood Cells
Healthy Volunteers
B-Lymphocytes
Research Design
Transplants

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Immunological Consequences of Interleukin 12 Administration after Autologous Stem Cell Transplantation. / Pelloso, David; Cyran, Katherine; Timmons, Lynette; Williams, Brian T.; Robertson, Michael.

In: Clinical Cancer Research, Vol. 10, No. 6, 15.03.2004, p. 1935-1942.

Research output: Contribution to journalArticle

Pelloso, David ; Cyran, Katherine ; Timmons, Lynette ; Williams, Brian T. ; Robertson, Michael. / Immunological Consequences of Interleukin 12 Administration after Autologous Stem Cell Transplantation. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 6. pp. 1935-1942.
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abstract = "Purpose: The purpose is to determine the immunological effects of recombinant human interleukin (rhIL)-12 therapy after autologous stem cell transplantation. Experimental Design: Twelve patients (8 non-Hodgkin's lymphoma, 2 Hodgkin's disease, and 2 plasma cell myeloma) were treated with rhIL-12 by bolus i.v. injection in doses of 30, 100, or 250 ng/kg starting at a median of 66 days post-transplant. Immunological assays were performed using serum and peripheral blood mononuclear cell (PBMC) samples obtained on study. Results: Dose-dependent increases in the total lymphocyte count occurred during rhIL-12 therapy. The absolute number of peripheral blood CD4 T cells increased up to 16.3-fold, CD8 T cells up to 20.5-fold, B cells up to 11-fold, and natural killer (NK) cells up to 12.3-fold during rhIL-12 administration and returned to pretreatment baseline levels after discontinuation of rhIL-12. CD56 bright NK cells expanded dramatically in the blood of a patient with baseline lymphopenia before rhIL-12 therapy. In vitro proliferation of patient PBMCs in response to IL-12 was indistinguishable from that of PBMCs obtained from healthy control subjects. Moreover, spontaneous in vitro proliferation of patient PBMCs increased significantly during rhIL-12 therapy. Increased levels of IFN-γ and IL-18 were detected in the serum of patients treated in the 100 and 250 ng/kg dose cohorts during the first multiple dose cycle. Conclusions: Expansion of T, B, and NK cells occurs in vivo during rhIL-12 therapy after autologous stem cell transplantation for hematological malignancies. In contrast to their striking defect in IL-12-induced IFN-γ production, posttransplant patient PBMCs exhibit normal proliferative responses to IL-12 in vitro. Additional investigation of rhIL-12 for posttransplantation immunotherapy is warranted.",
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AB - Purpose: The purpose is to determine the immunological effects of recombinant human interleukin (rhIL)-12 therapy after autologous stem cell transplantation. Experimental Design: Twelve patients (8 non-Hodgkin's lymphoma, 2 Hodgkin's disease, and 2 plasma cell myeloma) were treated with rhIL-12 by bolus i.v. injection in doses of 30, 100, or 250 ng/kg starting at a median of 66 days post-transplant. Immunological assays were performed using serum and peripheral blood mononuclear cell (PBMC) samples obtained on study. Results: Dose-dependent increases in the total lymphocyte count occurred during rhIL-12 therapy. The absolute number of peripheral blood CD4 T cells increased up to 16.3-fold, CD8 T cells up to 20.5-fold, B cells up to 11-fold, and natural killer (NK) cells up to 12.3-fold during rhIL-12 administration and returned to pretreatment baseline levels after discontinuation of rhIL-12. CD56 bright NK cells expanded dramatically in the blood of a patient with baseline lymphopenia before rhIL-12 therapy. In vitro proliferation of patient PBMCs in response to IL-12 was indistinguishable from that of PBMCs obtained from healthy control subjects. Moreover, spontaneous in vitro proliferation of patient PBMCs increased significantly during rhIL-12 therapy. Increased levels of IFN-γ and IL-18 were detected in the serum of patients treated in the 100 and 250 ng/kg dose cohorts during the first multiple dose cycle. Conclusions: Expansion of T, B, and NK cells occurs in vivo during rhIL-12 therapy after autologous stem cell transplantation for hematological malignancies. In contrast to their striking defect in IL-12-induced IFN-γ production, posttransplant patient PBMCs exhibit normal proliferative responses to IL-12 in vitro. Additional investigation of rhIL-12 for posttransplantation immunotherapy is warranted.

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