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
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • Toolbox: Coding and Computation
      • Toolbox: Signatures and Cells
      • "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
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • Toolbox: Coding and Computation
      • Toolbox: Signatures and Cells
      • "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

Clinical Trials of Cancer Immunotherapies

Abstract A010: Personalized neoantigen-targeting vaccines for high-risk melanoma generate epitope spreading

Zhuting Hu, Donna Leet, Siranush Sarkizova, Rebecca Holden, Jing Sun, Susan Klaeger, Karl R. Clauser, Sachet A. Shukla, Wandi Zhang, Steven A. Carr, Edward F. Fritsch, Bradley L. Pentelute, Nir Hacohen, Derin B. Keskin, Patrick A. Ott and Catherine J. Wu
Zhuting Hu
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Donna Leet
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Siranush Sarkizova
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rebecca Holden
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jing Sun
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan Klaeger
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karl R. Clauser
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sachet A. Shukla
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wandi Zhang
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven A. Carr
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edward F. Fritsch
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bradley L. Pentelute
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nir Hacohen
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Derin B. Keskin
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick A. Ott
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Catherine J. Wu
Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts Institute of Technology, Cambridge, MA; Broad Institute, Cambridge, MA; Neon Therapeutics, Cambridge, MA; Massachusetts General Hospital, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A010 Published February 2019
  • Article
  • Info & Metrics
Loading
Abstracts: Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; September 30 - October 3, 2018; New York, NY

Abstract

Cancer vaccines have been envisioned as a key tool for generating effective cancer therapy. Tumor neoantigens are ideal targets because of their exquisite tumor-specific expression (arising from somatic mutations of the tumor) and high level of immunogenicity (lacking of central tolerance against them). Recently, we and others have demonstrated that personalized neoantigen-targeting vaccines are safe, feasible and highly immunogenic in phase I trials of stage III/IV resected high-risk melanoma (Ott & Hu, Nature 2017; Sahin, Nature 2017). Our neoantigen vaccine (NeoVax), consisting of up to 20 long peptides and poly-ICLC, induced strong polyfunctional neoantigen-specific T-cells that recognized patient tumor in vitro. In addition, 2 patients who were vaccinated and received anti-PD1 checkpoint blockade (CPB) therapy upon relapse had durable complete responses (CRs). Thus far, these vaccine studies have been performed in the adjuvant setting, preventing direct assessment of on-target tumor killing in vivo due to the lack of evaluable tumor. On the other hand, the detection of epitope spreading (the broadening of the immune response from the initially targeted epitope to others) would indirectly suggest therapy-induced tumor lysis, whereby the release of additional tumor antigens leads to further tumor-specific T-cell activation. To explore the hypothesis that NeoVax+/- CPB generates epitope spreading, we evaluated the T-cell responses against neoantigens and tumor associated antigens (TAAs) that were not included in the original vaccine in 3 patients. We performed experiments for a patient with stage III melanoma who has remained disease-free (Pt.3) after vaccination and 2 patients with resected stage IV disease who recurred but achieved CR after CPB (Pts. 2&6). For the assessment of CD8+ T-cell responses, we designed 9-10 aa epitope length peptides (predicted by NetMHCpan and/or a mass spectrometry [MS]-based prediction algorithm (Abelin, Immunity 2017) or detected physically on the tumor’s surface class I complexes by MS) arising from 3 categories of antigens: (i) neoantigen peptides; (ii) TAA peptides based on high tumor gene expression; (iii) TAA peptides, detected on the tumor by MS (available for 2 of the 3 patients). For testing of CD4+ T-cell responses, we designed 15-16 aa peptides that spanned predicted neoepitopes from category i. Per patient, we designed peptides against up to 70 genes (~20 for each category). PBMCs from pre- , week 16 post-vaccination and post-CPB were stimulated with peptide pools (~10 peptides/pool) for 2 weeks, followed by restimulation with individual peptides in IFN-γ ELISPOT assays to deconvolute the peptides. Thus far, we have tested CD8+ T-cells against 71 neoantigens (category i) and 22 TAAs (ii) from Pts. 2 and 6, and CD4+ T-cells against 30 neoantigens from all 3 patients. We identified CD4+ T-cells specific for 3 peptides (mut-AGAP3 [Pt.2], -EYA3 and -P2RY4 [Pt.3]) in the week 16 samples that were not included in the original respective vaccines; these populations were expanded only post, but not pre-vaccination. For Pt.2, an additional CD4+ T-cell response against a different neoantigen peptide derived from mut-AGAP3 was detected only after CPB therapy. Lastly, all four lines of CD4+ T-cells reactive against these identified neoantigens were able to discriminate between the mutated and wild-type forms of the peptides, suggesting tumor specificity and lack of cross reactivity with normal tissues. Therefore, our results demonstrate that epitope spreading occurred in 2 patients after vaccination, and further spreading was detected in one of the two following CPB therapy. Ongoing studies are focused on screening additional peptides and investigating the association of epitope spreading and any residual tumor burden. The newly activated antigen-specific T-cells can target additional tumor antigens provided by epitope spreading, thus potentially enhancing therapeutic efficacy.

Citation Format: Zhuting Hu, Donna Leet, Siranush Sarkizova, Rebecca Holden, Jing Sun, Susan Klaeger, Karl R. Clauser, Sachet A. Shukla, Wandi Zhang, Steven A. Carr, Edward F. Fritsch, Bradley L. Pentelute, Nir Hacohen, Derin B. Keskin, Patrick A. Ott, Catherine J. Wu. Personalized neoantigen-targeting vaccines for high-risk melanoma generate epitope spreading [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A010.

  • ©2019 American Association for Cancer Research.
Previous
Back to top
Cancer Immunology Research: 7 (2 Supplement)
February 2019
Volume 7, Issue 2 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 A010: Personalized neoantigen-targeting vaccines for high-risk melanoma generate epitope spreading
(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 A010: Personalized neoantigen-targeting vaccines for high-risk melanoma generate epitope spreading
Zhuting Hu, Donna Leet, Siranush Sarkizova, Rebecca Holden, Jing Sun, Susan Klaeger, Karl R. Clauser, Sachet A. Shukla, Wandi Zhang, Steven A. Carr, Edward F. Fritsch, Bradley L. Pentelute, Nir Hacohen, Derin B. Keskin, Patrick A. Ott and Catherine J. Wu
Cancer Immunol Res February 1 2019 (7) (2 Supplement) A010; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A010

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract A010: Personalized neoantigen-targeting vaccines for high-risk melanoma generate epitope spreading
Zhuting Hu, Donna Leet, Siranush Sarkizova, Rebecca Holden, Jing Sun, Susan Klaeger, Karl R. Clauser, Sachet A. Shukla, Wandi Zhang, Steven A. Carr, Edward F. Fritsch, Bradley L. Pentelute, Nir Hacohen, Derin B. Keskin, Patrick A. Ott and Catherine J. Wu
Cancer Immunol Res February 1 2019 (7) (2 Supplement) A010; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A010
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

Clinical Trials of Cancer Immunotherapies

  • Abstract A007: Comparison of pretreatment conditioning on efficacy in two cohorts of a pilot study of genetically engineered NY-ESO-1c259T-cells in patients with synovial sarcoma
  • Abstract A006: Phase 1 study to evaluate the safety and tolerability of MEDI4736 (durvalumab, durva) + tremelimumab (treme) in patients with advanced solid tumors
Show more Clinical Trials of Cancer Immunotherapies

Clinical Trials of Cancer Immunotherapies: Poster Presentations - Proffered Abstracts

  • Abstract A007: Comparison of pretreatment conditioning on efficacy in two cohorts of a pilot study of genetically engineered NY-ESO-1c259T-cells in patients with synovial sarcoma
  • Abstract A006: Phase 1 study to evaluate the safety and tolerability of MEDI4736 (durvalumab, durva) + tremelimumab (treme) in patients with advanced solid tumors
  • Abstract A010: Personalized neoantigen-targeting vaccines for high-risk melanoma generate epitope spreading
Show more Clinical Trials of Cancer 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