Combination of epitope-optimized DNA vaccination and passive infusion of monoclonal antibody against HER2/neu leads to breast tumor regression in mice

Francesca Orlandi; José A Guevara-Patiño; Taha Merghoub; Jedd D Wolchok; Alan N Houghton; Polly D Gregor

doi:10.1016/j.vaccine.2011.03.017

Combination of epitope-optimized DNA vaccination and passive infusion of monoclonal antibody against HER2/neu leads to breast tumor regression in mice

Vaccine. 2011 May 9;29(20):3646-54. doi: 10.1016/j.vaccine.2011.03.017. Epub 2011 Mar 22.

Authors

Francesca Orlandi¹, José A Guevara-Patiño, Taha Merghoub, Jedd D Wolchok, Alan N Houghton, Polly D Gregor

Affiliation

¹ The Swim Across America Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, United States.

PMID: 21435405
DOI: 10.1016/j.vaccine.2011.03.017

Abstract

HER2/neu is an oncogene amplified and over-expressed in 20-30% of breast adenocarcinomas. Treatment with the humanized monoclonal antibody trastuzumab has shown efficacy in combination with cytotoxic agents, although resistance occurs over time. Novel approaches are needed to further increase antibody efficacy. In this study, we provide evidence in a mouse breast cancer therapeutic tumor model that the combination of active immunization with a modified HER2/neu DNA vaccine and passive infusion of an anti-HER2/neu monoclonal antibody leads to significant regression of established tumors. Our data indicate that combination therapy with a HER2/neu DNA vaccine and trastuzumab may have clinical activity in breast cancer patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / immunology
Adenocarcinoma / therapy
Animals
Antibodies, Monoclonal / administration & dosage
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / therapeutic use*
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / immunology
Cancer Vaccines / administration & dosage
Cancer Vaccines / immunology*
Epitopes / immunology*
Female
Immunotherapy
Lymphocytes, Tumor-Infiltrating / immunology
Mammary Neoplasms, Experimental / immunology
Mammary Neoplasms, Experimental / therapy*
Mice
Mice, Inbred BALB C
Mutagenesis, Site-Directed
Receptor, ErbB-2 / immunology*
Trastuzumab
Vaccines, DNA / administration & dosage
Vaccines, DNA / immunology

Substances

Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Cancer Vaccines
Epitopes
Vaccines, DNA
Receptor, ErbB-2
Trastuzumab