Article abstract
Nature Biotechnology 20, 70 - 75 (2002)
doi:10.1038/nbt0102-70
Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCR
/CD28 receptor
John Maher1, Renier J. Brentjens1, Gertrude Gunset1, Isabelle Rivière1 & Michel Sadelain1
Abstract
Artificial receptors provide a promising approach to target T lymphocytes to tumor antigens. However, the receptors described thus far produce either an activation or a co-stimulatory signal alone, thus limiting the spectrum of functions accomplished by the genetically modified cells. Here we show that human primary T lymphocytes expressing fusion receptors directed to prostate-specific membrane antigen (PSMA) and containing combined T-cell receptor-
(TCR), and CD28 signaling elements, effectively lyse tumor cells expressing PSMA. When stimulated by cell-surface PSMA, retrovirally transduced lymphocytes undergo robust proliferation, expanding by more than 2 logs in three weeks, and produce large amounts of interleukin-2 (IL-2). Importantly, the amplified cell populations retain their antigen-specific cytolytic activity. These data demonstrate that fusion receptors containing both TCR and CD28 signaling moieties are potent molecules able to redirect and amplify human T-cell responses. These findings have important implications for adoptive immunotherapy of cancer, especially in the context of tumor cells that fail to express major histocompatibility complex antigens and co-stimulatory molecules.
- Department of Human Genetics/Medicine, Gene Transfer and Somatic Cell Engineering Laboratory, and Immunology Program, Memorial Sloan–Kettering Cancer Center, New York, NY 10021.
Correspondence to: Michel Sadelain1 e-mail: m-sadelain@ski.mskcc.org
|
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated REVIEWS RESEARCH |
