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

Research output: Contribution to journalArticlepeer-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 languageEnglish (US)
Pages (from-to)1916-1925
Number of pages10
JournalCancer Biology and Therapy
Volume6
Issue number12
DOIs
StatePublished - 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.

Keywords

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

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