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Title:
A phase II trial of trastuzumab in combination with low-dose interleukin-2 (IL-2) in patients (PTS) with metastatic breast cancer (MBC) who have previously failed trastuzumab | Breast Cancer Research and Treatment
Description:
Trastuzumab mediates the lysis of HER2-expressing breast cancer cell lines by interleukin-2 (IL-2) primed natural killer (NK) cells. We hypothesized that IL-2 would augment the anti-tumor effects of trastuzumab in MBC in patients who had progressed on or within 12 months of receiving a trastuzumab-containing regimen. Secondary objectives were to measure antibody-directed cellular cytotoxicity (ADCC) against HER2 over-expressing target cells, and to measure serum cytokines. Patients received trastuzumab (4 mg/kg intravenously (IV)) every 2 weeks in combination with daily low-dose IL-2 (1 million IU/m2 subcutaneously (SC)) and pulsed intermediate-dose IL-2 (12 million IU/m2 SC). Samples were analyzed for NK cell expansion and ADCC against a HER2-positive breast cancer cell line. In addition, interferon-gamma (IFN-γ), mRNA expression in peripheral blood mononuclear cells (PBMC) and the following serum cytokines were measured: IFN-γ, monokine-induced by IFN-γ (MIG), and interferon-inducible protein ten (IP-10). The median number of treatment cycles was four (range 1–23) and the treatment was well tolerated. There were no objective responses. NK cells were not expanded and ADCC was not enhanced. Eight (62%) patients had a twofold or higher increase in mRNA transcript for IFN-γ, two (15%) patients had elevated serum levels of IFN-γ and 12 (92%) had increases angiogenic MIG and IP-10. In trastuzumab-refractory patients adding IL-2 did not produce responses and did not result in NK cell expansion. However, these patients had the ability to respond to IL-2 as evidenced by increases in IFN-γ transcripts and chemokines. The lack of NK cell expansion may explain the absence of clinical benefit.
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Keywords {🔍}
cancer, article, google, scholar, pubmed, cas, breast, cells, trastuzumab, patients, interleukin, cell, killer, res, carson, natural, clin, usa, university, treatment, phase, clinical, research, trial, combination, roda, caligiuri, ifnγ, access, parihar, response, doiccr, state, privacy, cookies, content, young, iii, human, tumor, van, ohio, columbus, publish, search, metastatic, mani, fleming, shapiro, cellular,
Topics {✒️}
month download article/chapter lymphokine-activated killer cells antibody-dependent cellular cytotoxicity her2-positive breast cancer her2-expressing breast cancer antibody-coated tumor cells ab-coated tumor cells 1 million iu/m2 subcutaneously nih/nci grants p30 interferon-inducible protein ten her2-specific cytotoxic activity neoadjuvant anti-her2 antibodies 12 million iu/m2 sc breast cancer cells natural killer cells nk cell expansion pulsed intermediate-dose il-2 ohio state university human breast cancer daily low-dose il-2 expressing target cells metastatic breast cancer full article pdf primed natural killer related subjects breast cancer targets previously failed trastuzumab privacy choices/manage cookies antibody-coated targets adam brufsky b-cell nk cells anti-tumor effects low-dose interleukin-2 national cancer institute adoptive immunotherapy van krieken jh cell-recruiting chemokines vitro cytotoxic effect combination immunotherapy intrinsic drug resistance amy stark ms nrsa t32 fellow phase ii trial her2/neu de vries ij de wilde pc de mulder ph article mani dendritic cells
Questions {❓}
- Arnould L, Gelly M, Penault-Llorca F, Benoit L, Bonnetain F, Migeon C, Cabaret V, Fermeaux V, Bertheau P, Garnier J, Jeannin JF, Coudert B (2006) Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?
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headline:A phase II trial of trastuzumab in combination with low-dose interleukin-2 (IL-2) in patients (PTS) with metastatic breast cancer (MBC) who have previously failed trastuzumab
description:Trastuzumab mediates the lysis of HER2-expressing breast cancer cell lines by interleukin-2 (IL-2) primed natural killer (NK) cells. We hypothesized that IL-2 would augment the anti-tumor effects of trastuzumab in MBC in patients who had progressed on or within 12 months of receiving a trastuzumab-containing regimen. Secondary objectives were to measure antibody-directed cellular cytotoxicity (ADCC) against HER2 over-expressing target cells, and to measure serum cytokines. Patients received trastuzumab (4 mg/kg intravenously (IV)) every 2 weeks in combination with daily low-dose IL-2 (1 million IU/m2 subcutaneously (SC)) and pulsed intermediate-dose IL-2 (12 million IU/m2 SC). Samples were analyzed for NK cell expansion and ADCC against a HER2-positive breast cancer cell line. In addition, interferon-gamma (IFN-γ), mRNA expression in peripheral blood mononuclear cells (PBMC) and the following serum cytokines were measured: IFN-γ, monokine-induced by IFN-γ (MIG), and interferon-inducible protein ten (IP-10). The median number of treatment cycles was four (range 1–23) and the treatment was well tolerated. There were no objective responses. NK cells were not expanded and ADCC was not enhanced. Eight (62%) patients had a twofold or higher increase in mRNA transcript for IFN-γ, two (15%) patients had elevated serum levels of IFN-γ and 12 (92%) had increases angiogenic MIG and IP-10. In trastuzumab-refractory patients adding IL-2 did not produce responses and did not result in NK cell expansion. However, these patients had the ability to respond to IL-2 as evidenced by increases in IFN-γ transcripts and chemokines. The lack of NK cell expansion may explain the absence of clinical benefit.
datePublished:2008-12-03T00:00:00Z
dateModified:2008-12-03T00:00:00Z
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Trastuzumab
Her-2/neu
Interleukin-2
Breast cancer
Clinical trial
Oncology
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headline:A phase II trial of trastuzumab in combination with low-dose interleukin-2 (IL-2) in patients (PTS) with metastatic breast cancer (MBC) who have previously failed trastuzumab
description:Trastuzumab mediates the lysis of HER2-expressing breast cancer cell lines by interleukin-2 (IL-2) primed natural killer (NK) cells. We hypothesized that IL-2 would augment the anti-tumor effects of trastuzumab in MBC in patients who had progressed on or within 12 months of receiving a trastuzumab-containing regimen. Secondary objectives were to measure antibody-directed cellular cytotoxicity (ADCC) against HER2 over-expressing target cells, and to measure serum cytokines. Patients received trastuzumab (4 mg/kg intravenously (IV)) every 2 weeks in combination with daily low-dose IL-2 (1 million IU/m2 subcutaneously (SC)) and pulsed intermediate-dose IL-2 (12 million IU/m2 SC). Samples were analyzed for NK cell expansion and ADCC against a HER2-positive breast cancer cell line. In addition, interferon-gamma (IFN-γ), mRNA expression in peripheral blood mononuclear cells (PBMC) and the following serum cytokines were measured: IFN-γ, monokine-induced by IFN-γ (MIG), and interferon-inducible protein ten (IP-10). The median number of treatment cycles was four (range 1–23) and the treatment was well tolerated. There were no objective responses. NK cells were not expanded and ADCC was not enhanced. Eight (62%) patients had a twofold or higher increase in mRNA transcript for IFN-γ, two (15%) patients had elevated serum levels of IFN-γ and 12 (92%) had increases angiogenic MIG and IP-10. In trastuzumab-refractory patients adding IL-2 did not produce responses and did not result in NK cell expansion. However, these patients had the ability to respond to IL-2 as evidenced by increases in IFN-γ transcripts and chemokines. The lack of NK cell expansion may explain the absence of clinical benefit.
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Trastuzumab
Her-2/neu
Interleukin-2
Breast cancer
Clinical trial
Oncology
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