An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer.

Loading...
Thumbnail Image

Date

2010-09

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

285
views
316
downloads

Citation Stats

Attention Stats

Abstract

Therapeutic anticancer vaccines are designed to boost patients' immune responses to tumors. One approach is to use a viral vector to deliver antigen to in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific neutralizing antibodies and suppressive cell populations such as Tregs remain great challenges to the efficacy of this approach. We report here that an alphavirus vector, packaged in virus-like replicon particles (VRP) and capable of efficiently infecting DCs, could be repeatedly administered to patients with metastatic cancer expressing the tumor antigen carcinoembryonic antigen (CEA) and that it overcame high titers of neutralizing antibodies and elevated Treg levels to induce clinically relevant CEA-specific T cell and antibody responses. The CEA-specific antibodies mediated antibody-dependent cellular cytotoxicity against tumor cells from human colorectal cancer metastases. In addition, patients with CEA-specific T cell responses exhibited longer overall survival. These data suggest that VRP-based vectors can overcome the presence of neutralizing antibodies to break tolerance to self antigen and may be clinically useful for immunotherapy in the setting of tumor-induced immunosuppression.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1172/JCI42672

Publication Info

Morse, MA, AC Hobeika, T Osada, P Berglund, B Hubby, S Negri, D Niedzwiecki, GR Devi, et al. (2010). An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer. J Clin Invest, 120(9). pp. 3234–3241. 10.1172/JCI42672 Retrieved from https://hdl.handle.net/10161/4330.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Hobeika

Amy Claudine Hobeika

Assistant Professor in Surgery
Osada

Takuya Osada

Adjunct Associate Professor in the Department of Surgery
Niedzwiecki

Donna Niedzwiecki

Professor of Biostatistics & Bioinformatics

Primary interests include clinical trials design and the design and analysis of biomarker and imaging studies especially in the areas of GI cancer, lymphoma, melanoma, transplant and cancer immunotherapy.

Devi

Gayathri R. Devi

Professor in Surgery

Dr. Devi’s research interests include functional genomics, anti-cancer drug discovery and development, mechanisms of cancer cell signaling, tumor immunity and applications thereof for overcoming therapeutic resistance in cancer.

The lab has established prostate, inflammatory breast cancer and ovarian cellular and tumor models.

Burnett

Bruce Kendall Burnett

Associate Professor in Medicine

I am the Director of Regulatory Affairs within the Duke Translational Medicine Institute.  This function provides regulatory, quality and preclinical GLP support for investigators here at Duke.

Lyerly

Herbert Kim Lyerly

George Barth Geller Distinguished Professor of Immunology

Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.