Engineering the TGFβ Receptor to Enhance the Therapeutic Potential of Natural Killer Cells as an Immunotherapy for Neuroblastoma
Abstract
The ability of natural killer (NK) cells to lyse allogeneic targets, without the need for explicit matching or priming, makes them an attractive platform for cell-based immunotherapy. Umbilical cord blood is a practical source for generating banks of such third-party NK cells for “off-the-shelf” cell therapy applications. NK cells are highly cytolytic, and their potent antitumor effects can be rapidly triggered by a lack of HLA expression on interacting target cells, as is the case for a majority of solid tumors, including neuroblastoma. Neuroblastoma is a leading cause of pediatric cancer–related deaths and an ideal candidate for NK-cell therapy. However, the antitumor efficacy of NK cells is limited by immunosuppressive cytokines in the tumor microenvironment, such as TGFβ, which impair NK cell function and survival.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 15, 2019
- Source ID
- 10.1158/1078-0432.ccr-18-3183
Entities
People
- C. Russell Y. Cruz
- Catherine M. Bollard
- Elizabeth Chorvinsky
- Eric Yvon
- Rachel A. Burga
- Rohan Fernandes
Organizations
- Children's National Hospital
- George Washington University
- United States Department of Defense