- Poster presentation
- Open Access
B7-h3-specific engager T cells for the immunotherapy of pediatric solid tumors
© DeRenzo et al. 2015
- Published: 4 November 2015
- High Grade Glioma
- Effector Function
- Internal Ribosomal Entry Site
B7-H3 positive tumors, including osteosarcoma, neuroblastoma, and high grade glioma, cause significant morbidity and mortality despite aggressive multimodality treatments. Current B7-H3-targeted immune-therapies take advantage of the monoclonal antibody 8H9, which is actively being evaluated in Phase I clinical trials. Engager T cells, which secrete bispecific engager molecules consisting of single chain variable fragments specific for CD3 and a tumor antigen, are a new class of antigen-specific T cells, with the unique ability to redirect bystander T cells to tumors, amplifying anti-tumor effects. The goal of this project was to develop B7-H3-specific Engager T cells, and pre-clinically evaluate their effector function in vitro and in vivo.
B7-H3-Engager T cells were generated by transducing T cells with a retroviral vector encoding a B7-H3-specific T cell engager and mOrange separated by an internal ribosomal entry site. B7-H3-Engager T cell effector function was then evaluated in vitro and in a metastatic osteosarcoma xenograft model.
We successfully generated B7-H3-Engager T cells and demonstrate that these cells recognize and kill B7-H3-positive tumor cells in an antigen-dependent manner, and have potent anti-osteosarcoma activity in vivo. Thus, B7-H3-Engager T cells may present a promising alternative to current T cell immunotherapy approaches for pediatric solid tumors.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.