| First Author | Klebanoff CA | Year | 2009 |
| Journal | Blood | Volume | 114 |
| Issue | 9 | Pages | 1776-83 |
| PubMed ID | 19561320 | Mgi Jnum | J:152256 |
| Mgi Id | MGI:4357733 | Doi | 10.1182/blood-2008-12-192419 |
| Citation | Klebanoff CA, et al. (2009) Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination. Blood 114(9):1776-83 |
| abstractText | Naive and memory CD8(+) T cells can undergo programmed activation and expansion in response to a short T-cell receptor stimulus, but the extent to which in vitro programming can qualitatively substitute for an in vivo antigen stimulation remains unknown. We show that self-/tumor-reactive effector memory CD8(+) T cells (T(EM)) programmed in vitro either with peptide-pulsed antigen-presenting cells or plate-bound anti-CD3/anti-CD28 embark on a highly stereotyped response of in vivo clonal expansion and tumor destruction nearly identical to that of vaccine-stimulated T(EM) cells. This programmed response was associated with an interval of antigen-independent interferon-gamma (IFN-gamma) release that facilitated the dynamic expression of the major histocompatibility complex class I restriction element H-2D(b) on responding tumor cells, leading to recognition and subsequent tumor lysis. Delaying cell transfer for more than 24 hours after stimulation or infusion of cells deficient in IFN-gamma entirely abrogated the benefit of the programmed response, whereas transfer of cells unable to respond to IFN-gamma had no detriment to antitumor immunity. These findings extend the phenomenon of a programmable effector response to memory CD8(+) T cells and have major implications for the design of current adoptive-cell transfer trials. |
