Title
CAR T-Cell Therapy: Progress and Prospects
UMMS Affiliation
Department of Pediatrics; Horae Gene Therapy Center
Publication Date
4-1-2017
Document Type
Article
Disciplines
Genetics and Genomics | Therapeutics
Abstract
Lentivirus-mediated transduction of autologous T cells with a chimeric antigen receptor (CAR) to confer a desired epitope specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance antitumor immunity have been less specific and less effective. These have included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes, recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells with tumor antigens. Unlike any of those methods, the engineering of CAR T cells combine specific monoclonal antibody gene sequences to confer epitope specificity and other T-cell receptor and activation domains to create a self-contained single vector approach to produce a very specific antitumor response, as is seen with CD19-directed CAR T cells used to treat CD19-expressing B-cell malignancies. Recent success with these therapies is the culmination of a long step-wise iterative process of improvement in the design of CAR vectors. This review aims to summarize this long series of advances in the development of effective CAR vector since their initial development in the 1990s, and to describe emerging approaches to design that promise to enhance and widen the human gene therapy relevance of CAR T-cell therapy in the future.
DOI of Published Version
10.1089/hgtb.2016.153
Source
Hum Gene Ther Methods. 2017 Apr;28(2):61-66. doi: 10.1089/hgtb.2016.153. Link to article on publisher's site
Journal/Book/Conference Title
Human gene therapy methods
Related Resources
PubMed ID
28330372
Repository Citation
Wilkins, Olivia; Keeler, Allison M.; and Flotte, Terence R., "CAR T-Cell Therapy: Progress and Prospects" (2017). Pediatric Publications and Presentations. 129.
https://escholarship.umassmed.edu/peds_pp/129