Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients

B. Petricevic, J. Laengle, J. Singer, M. Sachet, J. Singer, G. Steger, R. Bartsch, E. Jensen-Jarolim, M. Bergmann, Journal of Translational Medicine 11 (2013).

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Journal Article | Published | English
Author
Petricevic, Branka; Laengle, Johannes; Singer, Josef; Sachet, Monika; Singer, JuditIST Austria ; Steger, Guenther; Bartsch, Rupert; Jensen-Jarolim, Erika; Bergmann, Michael
Abstract
Background: Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy. Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological phenomena. Methods: We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS). Results: ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+ cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells. Conclusion: The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC and ADCP appears not to be affected by treatment duration, disease progression or concomitant chemotherapy. This finding supports the application of trastuzumab at any stage of the disease.
Publishing Year
Date Published
2013-12-12
Journal Title
Journal of Translational Medicine
Volume
11
Article Number
307
ISSN
IST-REx-ID

Cite this

Petricevic B, Laengle J, Singer J, et al. Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients. Journal of Translational Medicine. 2013;11. doi:10.1186/1479-5876-11-307
Petricevic, B., Laengle, J., Singer, J., Sachet, M., Singer, J., Steger, G., … Bergmann, M. (2013). Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients. Journal of Translational Medicine, 11. https://doi.org/10.1186/1479-5876-11-307
Petricevic, Branka, Johannes Laengle, Josef Singer, Monika Sachet, Judit Singer, Guenther Steger, Rupert Bartsch, Erika Jensen-Jarolim, and Michael Bergmann. “Trastuzumab Mediates Antibody-Dependent Cell-Mediated Cytotoxicity and Phagocytosis to the Same Extent in Both Adjuvant and Metastatic HER2/Neu Breast Cancer Patients.” Journal of Translational Medicine 11 (2013). https://doi.org/10.1186/1479-5876-11-307.
B. Petricevic et al., “Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients,” Journal of Translational Medicine, vol. 11, 2013.
Petricevic B, Laengle J, Singer J, Sachet M, Singer J, Steger G, Bartsch R, Jensen-Jarolim E, Bergmann M. 2013. Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients. Journal of Translational Medicine. 11.
Petricevic, Branka, et al. “Trastuzumab Mediates Antibody-Dependent Cell-Mediated Cytotoxicity and Phagocytosis to the Same Extent in Both Adjuvant and Metastatic HER2/Neu Breast Cancer Patients.” Journal of Translational Medicine, vol. 11, 307, Springer Nature, 2013, doi:10.1186/1479-5876-11-307.
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