Posttransplant Adoptive Immunotherapy With Activated Natural Killer Cells in Patients With Metastatic Breast Cancer

Margarida deMagalhaes-Silverman, Albert Donnenberg, Barry Lembersky, Elaine Elder, John Lister, Witold Rybka, Theresa Whiteside, Edward Ball

Research output: Contribution to journalArticle

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Abstract

Relapse after high-dose chemotherapy is the main cause of therapeutic failure in patients with metastatic breast cancer. Adoptive immunotherapy with interleukin-2 (IL-2) plus activated natural killer cells may eliminate residual disease without excessive toxicity. The authors sought to determine if immunotherapy immediately after transplantation would affect engraftment and the toxicity associated with transplantation. Fifteen consecutive patients with metastatic breast cancer were allocated to three cohorts. Cohort 1 (five patients) received high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by peripheral blood stem cell infusion and granulocyte colony-stimulating factor at 10 μg/kg. Cohort 2 (five patients) received in addition rhIL-2 (2 × 10 IU/m/day) for 4 days intravenously via continuous infusion after peripheral blood stem cell infusion. In cohort 3 (five patients), peripheral blood stem cell transplant was followed by infusion of autologous activated NK cells and rhIL-2 (2 × 10 IU/m/day) for 4 days (via continuous intravenous infusion). Generation of activated NK cells was possible in all patients in cohort 3. All patients has successful engraftment. Median time to absolute neutrophil count more than 0.5 × 10/L was 8 days (range, 8 to 11 days) in cohort 1, 9 days (range, 7 to 11 days) in cohort 2, and 9 days (range, 8 to 9 days) in cohort 3. Median time until the platelet count was more than 20 × 10/L was 14 days (range, 9 to 22 days) in cohort 1, 11 days (range, 6 to 14 days) in cohort 2, and 12 days (range, 11 to 21 days) in cohort 3. All patients developed neutropenic fevers, but the overall toxicity associated with the infusion of IL-2 (cohort 2) or IL-2 plus activated NK cells (cohort 3) did not differ from that observed in cohort 1. Complete responses were achieved in one patient in cohort 1, in two patients in cohort 2, and in one patient in cohort 3. In conclusion, post-transplant adoptive immunotherapy with activated NK cells plus IL-2 is feasible, well tolerated, and does not adversely affect engraftment.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalJournal of Immunotherapy
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2000

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Adoptive Immunotherapy
Natural Killer Cells
Breast Neoplasms
Interleukin-2
Transplantation
Thiotepa
Transplants
Carboplatin
Granulocyte Colony-Stimulating Factor
Platelet Count
Intravenous Infusions
Immunotherapy
Cyclophosphamide
Neutrophils
Fever

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

deMagalhaes-Silverman, Margarida ; Donnenberg, Albert ; Lembersky, Barry ; Elder, Elaine ; Lister, John ; Rybka, Witold ; Whiteside, Theresa ; Ball, Edward. / Posttransplant Adoptive Immunotherapy With Activated Natural Killer Cells in Patients With Metastatic Breast Cancer. In: Journal of Immunotherapy. 2000 ; Vol. 23, No. 1. pp. 154-160.
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abstract = "Relapse after high-dose chemotherapy is the main cause of therapeutic failure in patients with metastatic breast cancer. Adoptive immunotherapy with interleukin-2 (IL-2) plus activated natural killer cells may eliminate residual disease without excessive toxicity. The authors sought to determine if immunotherapy immediately after transplantation would affect engraftment and the toxicity associated with transplantation. Fifteen consecutive patients with metastatic breast cancer were allocated to three cohorts. Cohort 1 (five patients) received high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by peripheral blood stem cell infusion and granulocyte colony-stimulating factor at 10 μg/kg. Cohort 2 (five patients) received in addition rhIL-2 (2 × 10 IU/m/day) for 4 days intravenously via continuous infusion after peripheral blood stem cell infusion. In cohort 3 (five patients), peripheral blood stem cell transplant was followed by infusion of autologous activated NK cells and rhIL-2 (2 × 10 IU/m/day) for 4 days (via continuous intravenous infusion). Generation of activated NK cells was possible in all patients in cohort 3. All patients has successful engraftment. Median time to absolute neutrophil count more than 0.5 × 10/L was 8 days (range, 8 to 11 days) in cohort 1, 9 days (range, 7 to 11 days) in cohort 2, and 9 days (range, 8 to 9 days) in cohort 3. Median time until the platelet count was more than 20 × 10/L was 14 days (range, 9 to 22 days) in cohort 1, 11 days (range, 6 to 14 days) in cohort 2, and 12 days (range, 11 to 21 days) in cohort 3. All patients developed neutropenic fevers, but the overall toxicity associated with the infusion of IL-2 (cohort 2) or IL-2 plus activated NK cells (cohort 3) did not differ from that observed in cohort 1. Complete responses were achieved in one patient in cohort 1, in two patients in cohort 2, and in one patient in cohort 3. In conclusion, post-transplant adoptive immunotherapy with activated NK cells plus IL-2 is feasible, well tolerated, and does not adversely affect engraftment.",
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deMagalhaes-Silverman, M, Donnenberg, A, Lembersky, B, Elder, E, Lister, J, Rybka, W, Whiteside, T & Ball, E 2000, 'Posttransplant Adoptive Immunotherapy With Activated Natural Killer Cells in Patients With Metastatic Breast Cancer', Journal of Immunotherapy, vol. 23, no. 1, pp. 154-160. https://doi.org/10.1097/00002371-200001000-00018

Posttransplant Adoptive Immunotherapy With Activated Natural Killer Cells in Patients With Metastatic Breast Cancer. / deMagalhaes-Silverman, Margarida; Donnenberg, Albert; Lembersky, Barry; Elder, Elaine; Lister, John; Rybka, Witold; Whiteside, Theresa; Ball, Edward.

In: Journal of Immunotherapy, Vol. 23, No. 1, 01.01.2000, p. 154-160.

Research output: Contribution to journalArticle

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AU - deMagalhaes-Silverman, Margarida

AU - Donnenberg, Albert

AU - Lembersky, Barry

AU - Elder, Elaine

AU - Lister, John

AU - Rybka, Witold

AU - Whiteside, Theresa

AU - Ball, Edward

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AB - Relapse after high-dose chemotherapy is the main cause of therapeutic failure in patients with metastatic breast cancer. Adoptive immunotherapy with interleukin-2 (IL-2) plus activated natural killer cells may eliminate residual disease without excessive toxicity. The authors sought to determine if immunotherapy immediately after transplantation would affect engraftment and the toxicity associated with transplantation. Fifteen consecutive patients with metastatic breast cancer were allocated to three cohorts. Cohort 1 (five patients) received high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by peripheral blood stem cell infusion and granulocyte colony-stimulating factor at 10 μg/kg. Cohort 2 (five patients) received in addition rhIL-2 (2 × 10 IU/m/day) for 4 days intravenously via continuous infusion after peripheral blood stem cell infusion. In cohort 3 (five patients), peripheral blood stem cell transplant was followed by infusion of autologous activated NK cells and rhIL-2 (2 × 10 IU/m/day) for 4 days (via continuous intravenous infusion). Generation of activated NK cells was possible in all patients in cohort 3. All patients has successful engraftment. Median time to absolute neutrophil count more than 0.5 × 10/L was 8 days (range, 8 to 11 days) in cohort 1, 9 days (range, 7 to 11 days) in cohort 2, and 9 days (range, 8 to 9 days) in cohort 3. Median time until the platelet count was more than 20 × 10/L was 14 days (range, 9 to 22 days) in cohort 1, 11 days (range, 6 to 14 days) in cohort 2, and 12 days (range, 11 to 21 days) in cohort 3. All patients developed neutropenic fevers, but the overall toxicity associated with the infusion of IL-2 (cohort 2) or IL-2 plus activated NK cells (cohort 3) did not differ from that observed in cohort 1. Complete responses were achieved in one patient in cohort 1, in two patients in cohort 2, and in one patient in cohort 3. In conclusion, post-transplant adoptive immunotherapy with activated NK cells plus IL-2 is feasible, well tolerated, and does not adversely affect engraftment.

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