Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Immunology Research
Cancer Immunology Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Non-Checkpoint Immunotherapies

Abstract B069: The best is not enough—when it is alone: Current clinical doses of humanized anti-Her2 antibodies should be applied in combination to delay development of trastuzumab resistance by additively enhancing ADCC

Gábor Tóth, Árpád Szöőr, László Simon, Yosef Yarden, János Szöllősi and György Vereb
Gábor Tóth
1University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Árpád Szöőr
1University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
László Simon
1University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yosef Yarden
2Weizmann Institute of Science, Rehovot, Israel.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
János Szöllősi
1University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
György Vereb
1University of Debrecen, Debrecen, Hungary;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/2326-6066.IMM2016-B069 Published November 2016
  • Article
  • Info & Metrics
Loading
Abstracts: Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; September 25-28, 2016; New York, NY

Abstract

Although the recently concluded CLEOPATRA trial showed clinical benefits of combining trastuzumab and pertuzumab for treating HER2-positive metastatic breast cancer, trastuzumab monotherapy is still the mainstay in adjuvant settings. Since trastuzumab resistance occurs in over half of these cancers, we examined the mechanisms by which treatment of intrinsically trastuzumab-resistant and -sensitive tumors can benefit from the combination of these antibodies. F(ab')2 of both trastuzumab and pertuzumab were generated and validated in order to separately analyze antibody-dependent cell-mediated cytotoxicity (ADCC)-based and direct biological effects of the antibodies.Compared to monotherapy, combination of the two antibodies at clinically permitted doses enhanced the recruitment of natural killer cells responsible for ADCC, and significantly delayed the outgrowth of xenografts from intrinsically trastuzumab-resistant JIMT-1 cells. Antibody dose-response curves of in vitro ADCC showed that antibody-mediated killing can be saturated, and the two antibodies exert an additive effect at sub-saturation doses. Thus, the additive effect in vivo indicates that therapeutic tissue levels likely do not saturate ADCC. Additionally, isobole studies with the in vitro trastuzumab-sensitive BT-474 cells showed that the direct biological effect of combined treatment is additive, and surpasses the maximum effect of either monotherapy. Our results suggest the combined therapy is expected to give results that are superior to monotherapy, whatever the type of HER2-positive tumor may be.The combination of both antibodies at maximum clinically approved doses should thus be administered to patients to recruit maximum ADCC and cause maximum direct biological growth inhibition.

Citation Format: Gábor Tóth, Árpád Szöőr, László Simon, Yosef Yarden, János Szöllősi, György Vereb. The best is not enough—when it is alone: Current clinical doses of humanized anti-Her2 antibodies should be applied in combination to delay development of trastuzumab resistance by additively enhancing ADCC [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B069.

  • ©2016 American Association for Cancer Research.
Previous
Back to top
Cancer Immunology Research: 4 (11 Supplement)
November 2016
Volume 4, Issue 11 Supplement
  • Table of Contents

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Immunology Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract B069: The best is not enough—when it is alone: Current clinical doses of humanized anti-Her2 antibodies should be applied in combination to delay development of trastuzumab resistance by additively enhancing ADCC
(Your Name) has forwarded a page to you from Cancer Immunology Research
(Your Name) thought you would be interested in this article in Cancer Immunology Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Abstract B069: The best is not enough—when it is alone: Current clinical doses of humanized anti-Her2 antibodies should be applied in combination to delay development of trastuzumab resistance by additively enhancing ADCC
Gábor Tóth, Árpád Szöőr, László Simon, Yosef Yarden, János Szöllősi and György Vereb
Cancer Immunol Res November 1 2016 (4) (11 Supplement) B069; DOI: 10.1158/2326-6066.IMM2016-B069

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract B069: The best is not enough—when it is alone: Current clinical doses of humanized anti-Her2 antibodies should be applied in combination to delay development of trastuzumab resistance by additively enhancing ADCC
Gábor Tóth, Árpád Szöőr, László Simon, Yosef Yarden, János Szöllősi and György Vereb
Cancer Immunol Res November 1 2016 (4) (11 Supplement) B069; DOI: 10.1158/2326-6066.IMM2016-B069
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Non-Checkpoint Immunotherapies

  • Abstract IA24: New frontiers in oncolytic virus therapy
  • Abstract PR10: Small-molecule inhibitors of CD73 promote activation of human CD8+ T cells and have profound effects on tumor growth and immune parameters in experimental tumors
  • Abstract PR11: Neo-antigen landscape dynamics during human melanoma-T cell interactions
Show more Non-Checkpoint Immunotherapies

Non-Checkpoint Immunotherapies: Poster Presentations - Proffered Abstracts

  • Abstract IA24: New frontiers in oncolytic virus therapy
  • Abstract PR10: Small-molecule inhibitors of CD73 promote activation of human CD8+ T cells and have profound effects on tumor growth and immune parameters in experimental tumors
  • Abstract PR11: Neo-antigen landscape dynamics during human melanoma-T cell interactions
Show more Non-Checkpoint Immunotherapies: Poster Presentations - Proffered Abstracts
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Cancer Immunology Essentials

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Immunology Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Immunology Research
eISSN: 2326-6074
ISSN: 2326-6066

Advertisement