Generation of Her-2/neu vaccine utilizing idiotypic network cascade

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

doi:10.4161/cbt.6.12.4967

Generation of Her-2/neu vaccine utilizing idiotypic network cascade

Smarajit Pal
, Asim Saha
, Kartik Mohanty
, 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

10 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 overexpression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. The Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. Our strategy is active specific immunotherapy in which patients immunized with an anti-Id antibody mimicking Her-2/neu will generate sustained high titer Her-2/neu specific protective antibodies. We have used an anti-Her-2/neu murine monoclonal antibody 4D5 as the immunizing antibody (Ab1) against which monoclonal anti-Ids or Ab2s were generated in syngeneic mice. We have characterized one such anti-Id (Ab2) designated 6D12, which mimics a specific epitope of Her-2/neu as defined by Trastuzumab, and can be used as a surrogate antigen for Her-2/neu across the species barriers. Immunization of allogeneic mice or rabbits with 6D12 induced anti-anti-Id (Ab3), that specifically recognized Her-2/neu-positive tumor cells and lysed these cells in culture by antibody-dependent cellular cytotoxicity (ADCC). Monoclonal Ab3 generated in mice against 6D12 inhibited the proliferation of Her-2/neu-positive SK-BR-3 cells in vitro in a dose dependent fashion and delayed the growth of Her-2/neu transfected EL4-Her-2 cells in vivo. These data suggest the potential use of 6D12 as a vaccine for Her-2/neu-positive human cancer.

Original language	English (US)
Pages (from-to)	1916-1925
Number of pages	10
Journal	Cancer Biology and Therapy
Volume	6
Issue number	12
DOIs	https://doi.org/10.4161/cbt.6.12.4967
State	Published - Dec 2007

Bibliographical note

Funding Information:
We would like to thank Dr. Joseph D. Rosen-blatt (University of Miami, Miami, FL) for providing the EL4-Her-2 cell line. 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.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Anti-idiotype antibody
Anti-tumor immunity
Breast cancer
Her-2/neu
Idiotypic cascade
Therapy
Vaccines

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10.4161/cbt.6.12.4967

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title = "Generation of Her-2/neu vaccine utilizing idiotypic network cascade",

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 overexpression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. The Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. Our strategy is active specific immunotherapy in which patients immunized with an anti-Id antibody mimicking Her-2/neu will generate sustained high titer Her-2/neu specific protective antibodies. We have used an anti-Her-2/neu murine monoclonal antibody 4D5 as the immunizing antibody (Ab1) against which monoclonal anti-Ids or Ab2s were generated in syngeneic mice. We have characterized one such anti-Id (Ab2) designated 6D12, which mimics a specific epitope of Her-2/neu as defined by Trastuzumab, and can be used as a surrogate antigen for Her-2/neu across the species barriers. Immunization of allogeneic mice or rabbits with 6D12 induced anti-anti-Id (Ab3), that specifically recognized Her-2/neu-positive tumor cells and lysed these cells in culture by antibody-dependent cellular cytotoxicity (ADCC). Monoclonal Ab3 generated in mice against 6D12 inhibited the proliferation of Her-2/neu-positive SK-BR-3 cells in vitro in a dose dependent fashion and delayed the growth of Her-2/neu transfected EL4-Her-2 cells in vivo. These data suggest the potential use of 6D12 as a vaccine for Her-2/neu-positive human cancer.",

keywords = "Anti-idiotype antibody, Anti-tumor immunity, Breast cancer, Her-2/neu, Idiotypic cascade, Therapy, Vaccines",

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

note = "Funding Information: We would like to thank Dr. Joseph D. Rosen-blatt (University of Miami, Miami, FL) for providing the EL4-Her-2 cell line. 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.",

year = "2007",

month = dec,

doi = "10.4161/cbt.6.12.4967",

language = "English (US)",

volume = "6",

pages = "1916--1925",

journal = "Cancer Biology and Therapy",

issn = "1538-4047",

publisher = "Taylor and Francis Ltd.",

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TY - JOUR

T1 - Generation of Her-2/neu vaccine utilizing idiotypic network cascade

AU - Pal, Smarajit

AU - Saha, Asim

AU - Mohanty, Kartik

AU - Mallick, Palash

AU - Chatterjee, Sunil K.

AU - Foon, Kenneth A.

AU - Bhattacharya-Chatterjee, Malaya

N1 - Funding Information: We would like to thank Dr. Joseph D. Rosen-blatt (University of Miami, Miami, FL) for providing the EL4-Her-2 cell line. 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 - 2007/12

Y1 - 2007/12

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 overexpression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. The Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. Our strategy is active specific immunotherapy in which patients immunized with an anti-Id antibody mimicking Her-2/neu will generate sustained high titer Her-2/neu specific protective antibodies. We have used an anti-Her-2/neu murine monoclonal antibody 4D5 as the immunizing antibody (Ab1) against which monoclonal anti-Ids or Ab2s were generated in syngeneic mice. We have characterized one such anti-Id (Ab2) designated 6D12, which mimics a specific epitope of Her-2/neu as defined by Trastuzumab, and can be used as a surrogate antigen for Her-2/neu across the species barriers. Immunization of allogeneic mice or rabbits with 6D12 induced anti-anti-Id (Ab3), that specifically recognized Her-2/neu-positive tumor cells and lysed these cells in culture by antibody-dependent cellular cytotoxicity (ADCC). Monoclonal Ab3 generated in mice against 6D12 inhibited the proliferation of Her-2/neu-positive SK-BR-3 cells in vitro in a dose dependent fashion and delayed the growth of Her-2/neu transfected EL4-Her-2 cells in vivo. These data suggest the potential use of 6D12 as a vaccine for Her-2/neu-positive human cancer.

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 overexpression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. The Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. Our strategy is active specific immunotherapy in which patients immunized with an anti-Id antibody mimicking Her-2/neu will generate sustained high titer Her-2/neu specific protective antibodies. We have used an anti-Her-2/neu murine monoclonal antibody 4D5 as the immunizing antibody (Ab1) against which monoclonal anti-Ids or Ab2s were generated in syngeneic mice. We have characterized one such anti-Id (Ab2) designated 6D12, which mimics a specific epitope of Her-2/neu as defined by Trastuzumab, and can be used as a surrogate antigen for Her-2/neu across the species barriers. Immunization of allogeneic mice or rabbits with 6D12 induced anti-anti-Id (Ab3), that specifically recognized Her-2/neu-positive tumor cells and lysed these cells in culture by antibody-dependent cellular cytotoxicity (ADCC). Monoclonal Ab3 generated in mice against 6D12 inhibited the proliferation of Her-2/neu-positive SK-BR-3 cells in vitro in a dose dependent fashion and delayed the growth of Her-2/neu transfected EL4-Her-2 cells in vivo. These data suggest the potential use of 6D12 as a vaccine for Her-2/neu-positive human cancer.

KW - Anti-idiotype antibody

KW - Anti-tumor immunity

KW - Breast cancer

KW - Her-2/neu

KW - Idiotypic cascade

KW - Therapy

KW - Vaccines

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DO - 10.4161/cbt.6.12.4967

M3 - Article

C2 - 18059165

AN - SCOPUS:42549162931

SN - 1538-4047

VL - 6

SP - 1916

EP - 1925

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

IS - 12

ER -

Generation of Her-2/neu vaccine utilizing idiotypic network cascade

Abstract

Bibliographical note

UN SDGs

Keywords

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