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Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells

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Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells. / Karagiannis, Panagiotis; Singer, Josef; Hunt, James; Gan, Samuel K E; Rudman, Sarah M; Mechtcheriakova, Diana; Knittelfelder, Regina; Daniels, Tracy R; Hobson, Philip S; Beavil, Andrew J; Spicer, James; Nestle, Frank O; Penichet, Manuel L; Gould, Hannah J; Jensen-Jarolim, Erika; Karagiannis, Sophia N.

In: CANCER IMMUNOL IMMUN, Vol. 58, No. 6, 06.2009, p. 915-30.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Karagiannis, P, Singer, J, Hunt, J, Gan, SKE, Rudman, SM, Mechtcheriakova, D, Knittelfelder, R, Daniels, TR, Hobson, PS, Beavil, AJ, Spicer, J, Nestle, FO, Penichet, ML, Gould, HJ, Jensen-Jarolim, E & Karagiannis, SN 2009, 'Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells', CANCER IMMUNOL IMMUN, vol. 58, no. 6, pp. 915-30. https://doi.org/10.1007/s00262-008-0607-1

APA

Karagiannis, P., Singer, J., Hunt, J., Gan, S. K. E., Rudman, S. M., Mechtcheriakova, D., Knittelfelder, R., Daniels, T. R., Hobson, P. S., Beavil, A. J., Spicer, J., Nestle, F. O., Penichet, M. L., Gould, H. J., Jensen-Jarolim, E., & Karagiannis, S. N. (2009). Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells. CANCER IMMUNOL IMMUN, 58(6), 915-30. https://doi.org/10.1007/s00262-008-0607-1

Vancouver

Karagiannis P, Singer J, Hunt J, Gan SKE, Rudman SM, Mechtcheriakova D et al. Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells. CANCER IMMUNOL IMMUN. 2009 Jun;58(6):915-30. https://doi.org/10.1007/s00262-008-0607-1

Bibtex

@article{6829ffb511904e6f8eef44e94c8bd52e,
title = "Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells",
abstract = "Trastuzumab (Herceptin), a humanized IgG1 antibody raised against the human epidermal growth factor receptor 2 (HER2/neu), is the main antibody in clinical use against breast cancer. Pre-clinical evidence and clinical studies indicate that trastuzumab employs several anti-tumour mechanisms that most likely contribute to enhanced survival of patients with HER2/neu-positive breast carcinomas. New strategies are aimed at improving antibody-based therapeutics like trastuzumab, e.g. by enhancing antibody-mediated effector function mechanisms. Based on our previous findings that a chimaeric ovarian tumour antigen-specific IgE antibody showed greater efficacy in tumour cell killing, compared to the corresponding IgG1 antibody, we have produced an IgE homologue of trastuzumab. Trastuzumab IgE was engineered with the same light- and heavy-chain variable-regions as trastuzumab, but with an epsilon in place of the gamma-1 heavy-chain constant region. We describe the physical characterisation and ligand binding properties of the trastuzumab IgE and elucidate its potential anti-tumour activities in functional assays. Both trastuzumab and trastuzumab IgE can activate monocytic cells to kill tumour cells, but they operate by different mechanisms: trastuzumab functions in antibody-dependent cell-mediated phagocytosis (ADCP), whereas trastuzumab IgE functions in antibody-dependent cell-mediated cytotoxicity (ADCC). Trastuzumab IgE, incubated with mast cells and HER2/neu-expressing tumour cells, triggers mast cell degranulation, recruiting against cancer cells a potent immune response, characteristic of allergic reactions. Finally, in viability assays both antibodies mediate comparable levels of tumour cell growth arrest. These functional characteristics of trastuzumab IgE, some distinct from those of trastuzumab, indicate its potential to complement or improve upon the existing clinical benefits of trastuzumab.",
keywords = "Antibodies, Monoclonal/therapeutic use, Antibodies, Monoclonal, Humanized, Antibody-Dependent Cell Cytotoxicity/drug effects, Antineoplastic Agents/therapeutic use, Breast Neoplasms/drug therapy, Cell Survival/drug effects, Cells, Cultured, Female, Flow Cytometry, Humans, Immunoglobulin E/immunology, Monocytes/cytology, Phagocytosis, Protein Engineering, Receptor, ErbB-2/immunology, Receptors, IgE/immunology, Trastuzumab",
author = "Panagiotis Karagiannis and Josef Singer and James Hunt and Gan, {Samuel K E} and Rudman, {Sarah M} and Diana Mechtcheriakova and Regina Knittelfelder and Daniels, {Tracy R} and Hobson, {Philip S} and Beavil, {Andrew J} and James Spicer and Nestle, {Frank O} and Penichet, {Manuel L} and Gould, {Hannah J} and Erika Jensen-Jarolim and Karagiannis, {Sophia N}",
year = "2009",
month = jun,
doi = "10.1007/s00262-008-0607-1",
language = "English",
volume = "58",
pages = "915--30",
journal = "CANCER IMMUNOL IMMUN",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "6",

}

RIS

TY - JOUR

T1 - Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells

AU - Karagiannis, Panagiotis

AU - Singer, Josef

AU - Hunt, James

AU - Gan, Samuel K E

AU - Rudman, Sarah M

AU - Mechtcheriakova, Diana

AU - Knittelfelder, Regina

AU - Daniels, Tracy R

AU - Hobson, Philip S

AU - Beavil, Andrew J

AU - Spicer, James

AU - Nestle, Frank O

AU - Penichet, Manuel L

AU - Gould, Hannah J

AU - Jensen-Jarolim, Erika

AU - Karagiannis, Sophia N

PY - 2009/6

Y1 - 2009/6

N2 - Trastuzumab (Herceptin), a humanized IgG1 antibody raised against the human epidermal growth factor receptor 2 (HER2/neu), is the main antibody in clinical use against breast cancer. Pre-clinical evidence and clinical studies indicate that trastuzumab employs several anti-tumour mechanisms that most likely contribute to enhanced survival of patients with HER2/neu-positive breast carcinomas. New strategies are aimed at improving antibody-based therapeutics like trastuzumab, e.g. by enhancing antibody-mediated effector function mechanisms. Based on our previous findings that a chimaeric ovarian tumour antigen-specific IgE antibody showed greater efficacy in tumour cell killing, compared to the corresponding IgG1 antibody, we have produced an IgE homologue of trastuzumab. Trastuzumab IgE was engineered with the same light- and heavy-chain variable-regions as trastuzumab, but with an epsilon in place of the gamma-1 heavy-chain constant region. We describe the physical characterisation and ligand binding properties of the trastuzumab IgE and elucidate its potential anti-tumour activities in functional assays. Both trastuzumab and trastuzumab IgE can activate monocytic cells to kill tumour cells, but they operate by different mechanisms: trastuzumab functions in antibody-dependent cell-mediated phagocytosis (ADCP), whereas trastuzumab IgE functions in antibody-dependent cell-mediated cytotoxicity (ADCC). Trastuzumab IgE, incubated with mast cells and HER2/neu-expressing tumour cells, triggers mast cell degranulation, recruiting against cancer cells a potent immune response, characteristic of allergic reactions. Finally, in viability assays both antibodies mediate comparable levels of tumour cell growth arrest. These functional characteristics of trastuzumab IgE, some distinct from those of trastuzumab, indicate its potential to complement or improve upon the existing clinical benefits of trastuzumab.

AB - Trastuzumab (Herceptin), a humanized IgG1 antibody raised against the human epidermal growth factor receptor 2 (HER2/neu), is the main antibody in clinical use against breast cancer. Pre-clinical evidence and clinical studies indicate that trastuzumab employs several anti-tumour mechanisms that most likely contribute to enhanced survival of patients with HER2/neu-positive breast carcinomas. New strategies are aimed at improving antibody-based therapeutics like trastuzumab, e.g. by enhancing antibody-mediated effector function mechanisms. Based on our previous findings that a chimaeric ovarian tumour antigen-specific IgE antibody showed greater efficacy in tumour cell killing, compared to the corresponding IgG1 antibody, we have produced an IgE homologue of trastuzumab. Trastuzumab IgE was engineered with the same light- and heavy-chain variable-regions as trastuzumab, but with an epsilon in place of the gamma-1 heavy-chain constant region. We describe the physical characterisation and ligand binding properties of the trastuzumab IgE and elucidate its potential anti-tumour activities in functional assays. Both trastuzumab and trastuzumab IgE can activate monocytic cells to kill tumour cells, but they operate by different mechanisms: trastuzumab functions in antibody-dependent cell-mediated phagocytosis (ADCP), whereas trastuzumab IgE functions in antibody-dependent cell-mediated cytotoxicity (ADCC). Trastuzumab IgE, incubated with mast cells and HER2/neu-expressing tumour cells, triggers mast cell degranulation, recruiting against cancer cells a potent immune response, characteristic of allergic reactions. Finally, in viability assays both antibodies mediate comparable levels of tumour cell growth arrest. These functional characteristics of trastuzumab IgE, some distinct from those of trastuzumab, indicate its potential to complement or improve upon the existing clinical benefits of trastuzumab.

KW - Antibodies, Monoclonal/therapeutic use

KW - Antibodies, Monoclonal, Humanized

KW - Antibody-Dependent Cell Cytotoxicity/drug effects

KW - Antineoplastic Agents/therapeutic use

KW - Breast Neoplasms/drug therapy

KW - Cell Survival/drug effects

KW - Cells, Cultured

KW - Female

KW - Flow Cytometry

KW - Humans

KW - Immunoglobulin E/immunology

KW - Monocytes/cytology

KW - Phagocytosis

KW - Protein Engineering

KW - Receptor, ErbB-2/immunology

KW - Receptors, IgE/immunology

KW - Trastuzumab

U2 - 10.1007/s00262-008-0607-1

DO - 10.1007/s00262-008-0607-1

M3 - SCORING: Journal article

C2 - 18941743

VL - 58

SP - 915

EP - 930

JO - CANCER IMMUNOL IMMUN

JF - CANCER IMMUNOL IMMUN

SN - 0340-7004

IS - 6

ER -