Humoral Epitope-Spreading Following Immunization with a HER-2/neu Peptide Based Vaccine in Cancer Patients

Mary L. Disis; Vivian Goodell; Kathy Schiffman; Keith L. Knutson

doi:10.1023/B:JOCI.0000040928.67495.52

Humoral Epitope-Spreading Following Immunization with a HER-2/neu Peptide Based Vaccine in Cancer Patients

Mary L. Disis, Vivian Goodell, Kathy Schiffman, Keith L. Knutson

Jacksonville, FL

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

99 Scopus citations

Abstract

HER-2/neu is a tumor antigen in patients with breast and ovarian cancer. Multiple varieties of vaccine strategies are being developed to immunize patients against HER-2/neu. Studies in animal models have demonstrated both T cell and antibody immunity are needed to mediate an antitumor response. Thirty-five patients, immunized with HER-2/neu peptide based vaccines, were evaluated for the generation of HER-2/neu-specific antibody immunity. Sixty percent of patients developed HER-2/neu IgG specific antibody responses to at least one peptide included in their vaccine. Twenty-nine percent of patients developed IgG immunity to the native HER-2/neu protein after peptide immunization. Humoral intramolecular epitope-spreading within the HER-2/neu protein occurred in 49% of immunized patients. Intermolecular epitope-spreading to p53 was evident in 20% of vaccinated patients. Of those patients who developed new immunity to p53, 71% had demonstrated antibody epitope-spreading within HER-2/neu.

Original language	English (US)
Pages (from-to)	571-578
Number of pages	8
Journal	Journal of Clinical Immunology
Volume	24
Issue number	5
DOIs	https://doi.org/10.1023/B:JOCI.0000040928.67495.52
State	Published - Sep 2004

Keywords

Antibody
HER-2/neu
breast
epitope-spreading
ovarian
vaccine

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1023/B:JOCI.0000040928.67495.52

Cite this

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title = "Humoral Epitope-Spreading Following Immunization with a HER-2/neu Peptide Based Vaccine in Cancer Patients",

abstract = "HER-2/neu is a tumor antigen in patients with breast and ovarian cancer. Multiple varieties of vaccine strategies are being developed to immunize patients against HER-2/neu. Studies in animal models have demonstrated both T cell and antibody immunity are needed to mediate an antitumor response. Thirty-five patients, immunized with HER-2/neu peptide based vaccines, were evaluated for the generation of HER-2/neu-specific antibody immunity. Sixty percent of patients developed HER-2/neu IgG specific antibody responses to at least one peptide included in their vaccine. Twenty-nine percent of patients developed IgG immunity to the native HER-2/neu protein after peptide immunization. Humoral intramolecular epitope-spreading within the HER-2/neu protein occurred in 49% of immunized patients. Intermolecular epitope-spreading to p53 was evident in 20% of vaccinated patients. Of those patients who developed new immunity to p53, 71% had demonstrated antibody epitope-spreading within HER-2/neu.",

keywords = "Antibody, HER-2/neu, breast, epitope-spreading, ovarian, vaccine",

author = "Disis, {Mary L.} and Vivian Goodell and Kathy Schiffman and Knutson, {Keith L.}",

note = "Funding Information: This work is supported for MLD by grants from the NIH, NCI (K08 CA61834 and R01 CA75163, U54 CA090818), the Cancer Research Treatment Foundation, and the Avon Foundation and for KLK by a fellowship from the Department of Defense Breast Cancer Program, DAMD17-00-1-0492, as well as DAMD17-03-1-0727. Patient care was conducted through the Clinical Research Center Facility at the University of Washington that is supported through NIH grant MO1-RR-00037. We are grateful for the nursing care of Donna Davis, R.N., and assistance in manuscript preparation by Ms Chalie Livingston and Mr Robert Schroeder. Our heartfelt thanks to all the patients who agreed to participate in this study.",

year = "2004",

month = sep,

doi = "10.1023/B:JOCI.0000040928.67495.52",

language = "English (US)",

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AU - Goodell, Vivian

AU - Schiffman, Kathy

AU - Knutson, Keith L.

N1 - Funding Information: This work is supported for MLD by grants from the NIH, NCI (K08 CA61834 and R01 CA75163, U54 CA090818), the Cancer Research Treatment Foundation, and the Avon Foundation and for KLK by a fellowship from the Department of Defense Breast Cancer Program, DAMD17-00-1-0492, as well as DAMD17-03-1-0727. Patient care was conducted through the Clinical Research Center Facility at the University of Washington that is supported through NIH grant MO1-RR-00037. We are grateful for the nursing care of Donna Davis, R.N., and assistance in manuscript preparation by Ms Chalie Livingston and Mr Robert Schroeder. Our heartfelt thanks to all the patients who agreed to participate in this study.

PY - 2004/9

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N2 - HER-2/neu is a tumor antigen in patients with breast and ovarian cancer. Multiple varieties of vaccine strategies are being developed to immunize patients against HER-2/neu. Studies in animal models have demonstrated both T cell and antibody immunity are needed to mediate an antitumor response. Thirty-five patients, immunized with HER-2/neu peptide based vaccines, were evaluated for the generation of HER-2/neu-specific antibody immunity. Sixty percent of patients developed HER-2/neu IgG specific antibody responses to at least one peptide included in their vaccine. Twenty-nine percent of patients developed IgG immunity to the native HER-2/neu protein after peptide immunization. Humoral intramolecular epitope-spreading within the HER-2/neu protein occurred in 49% of immunized patients. Intermolecular epitope-spreading to p53 was evident in 20% of vaccinated patients. Of those patients who developed new immunity to p53, 71% had demonstrated antibody epitope-spreading within HER-2/neu.

AB - HER-2/neu is a tumor antigen in patients with breast and ovarian cancer. Multiple varieties of vaccine strategies are being developed to immunize patients against HER-2/neu. Studies in animal models have demonstrated both T cell and antibody immunity are needed to mediate an antitumor response. Thirty-five patients, immunized with HER-2/neu peptide based vaccines, were evaluated for the generation of HER-2/neu-specific antibody immunity. Sixty percent of patients developed HER-2/neu IgG specific antibody responses to at least one peptide included in their vaccine. Twenty-nine percent of patients developed IgG immunity to the native HER-2/neu protein after peptide immunization. Humoral intramolecular epitope-spreading within the HER-2/neu protein occurred in 49% of immunized patients. Intermolecular epitope-spreading to p53 was evident in 20% of vaccinated patients. Of those patients who developed new immunity to p53, 71% had demonstrated antibody epitope-spreading within HER-2/neu.

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Humoral Epitope-Spreading Following Immunization with a HER-2/neu Peptide Based Vaccine in Cancer Patients

Abstract

Keywords

ASJC Scopus subject areas

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