Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu

Kartik Mohanty; Asim Saha; Smarajit Pal; Palash Mallick; Sunil K. Chatterjee; Kenneth A. Foon; Malaya Bhattacharya-Chatterjee

doi:10.1007/s10549-006-9391-9

Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu

Kartik Mohanty, Asim Saha, Smarajit Pal, Palash Mallick, Sunil K. Chatterjee, Kenneth A. Foon, Malaya Bhattacharya-Chatterjee

Pediatric Blood & Marrow Transplant & Cellular Therapy

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund's adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors.

Original language	English (US)
Pages (from-to)	1-11
Number of pages	11
Journal	Breast Cancer Research and Treatment
Volume	104
Issue number	1
DOIs	https://doi.org/10.1007/s10549-006-9391-9
State	Published - Jul 2007

Bibliographical note

Funding Information:
Acknowledgements We would like to thank Dr. Joseph D. Rosenblatt (Department of Medicine, University of Miami School of Medicine, Miami, FL) for providing the EL4-Her-2 cells. We also like to thank Mary B. Palascak and Peter Ciraolo for help in flow cytometry. This work was supported by the NIH Grant RO1 CA91878.

Keywords

Anti-idiotype antibody
Breast cancer
Her-2/neu
Murine model
Vaccines

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu",

abstract = "Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund's adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors.",

keywords = "Anti-idiotype antibody, Breast cancer, Her-2/neu, Murine model, Vaccines",

author = "Kartik Mohanty and Asim Saha and Smarajit Pal and Palash Mallick and Chatterjee, {Sunil K.} and Foon, {Kenneth A.} and Malaya Bhattacharya-Chatterjee",

note = "Funding Information: Acknowledgements We would like to thank Dr. Joseph D. Rosenblatt (Department of Medicine, University of Miami School of Medicine, Miami, FL) for providing the EL4-Her-2 cells. We also like to thank Mary B. Palascak and Peter Ciraolo for help in flow cytometry. This work was supported by the NIH Grant RO1 CA91878.",

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doi = "10.1007/s10549-006-9391-9",

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AU - Mohanty, Kartik

AU - Saha, Asim

AU - Pal, Smarajit

AU - Mallick, Palash

AU - Chatterjee, Sunil K.

AU - Foon, Kenneth A.

AU - Bhattacharya-Chatterjee, Malaya

N1 - Funding Information: Acknowledgements We would like to thank Dr. Joseph D. Rosenblatt (Department of Medicine, University of Miami School of Medicine, Miami, FL) for providing the EL4-Her-2 cells. We also like to thank Mary B. Palascak and Peter Ciraolo for help in flow cytometry. This work was supported by the NIH Grant RO1 CA91878.

PY - 2007/7

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N2 - Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund's adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors.

AB - Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund's adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors.

KW - Anti-idiotype antibody

KW - Breast cancer

KW - Her-2/neu

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Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu

Abstract

Bibliographical note

Keywords

UN SDGs

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