Abstract
Adoptive T-cell therapy with CD8+ CTLs is often characterized by poor persistence of the transferred T cells and limited effector responses. Improved persistence and therapeutic efficacy have been noted when antigen-activated CD8+ T cells express properties of memory cells. The current study was undertaken to more precisely characterize the development of memory-like CD8+ T cells from short-term CTLs in vitro and upon transfer in vivo, including their antitumor activity. Ovalbumin (OVA)-specific OT-I CTLs acquired phenotypic and functional properties of memory cells 2 to 3 days later either by lowering the concentration of antigen to a level that does not support primary responses and providing a survival signal through transgenic Bcl-2 in vitro or simply by transferring early day 3 CTLs to antigen-free lymphoid-replete mice. In lymphoid-replete mice, established OVA-expressing E.G7 tumor was rejected by short-term CTLs that simultaneously acquired memory-like properties in secondary lymphoid tissues, where tumor antigen level remained low. Collectively, these data indicate that CTLs readily converted to memory-like cells upon lowering antigen to a concentration that selectively supports memory responses and suggest that such conversion predicts successful adoptive immunotherapy.
| Original language | English |
|---|---|
| Pages (from-to) | 2984-2992 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 68 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 15 2008 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Modeling the CD8+ T effector to memory transition in adoptive T-cell antitumor immunotherapy. / Rolle, Cleo E.; Carrio, Roberto; Malek, Thomas.
In: Cancer Research, Vol. 68, No. 8, 15.04.2008, p. 2984-2992.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modeling the CD8+ T effector to memory transition in adoptive T-cell antitumor immunotherapy
AU - Rolle, Cleo E.
AU - Carrio, Roberto
AU - Malek, Thomas
PY - 2008/4/15
Y1 - 2008/4/15
N2 - Adoptive T-cell therapy with CD8+ CTLs is often characterized by poor persistence of the transferred T cells and limited effector responses. Improved persistence and therapeutic efficacy have been noted when antigen-activated CD8+ T cells express properties of memory cells. The current study was undertaken to more precisely characterize the development of memory-like CD8+ T cells from short-term CTLs in vitro and upon transfer in vivo, including their antitumor activity. Ovalbumin (OVA)-specific OT-I CTLs acquired phenotypic and functional properties of memory cells 2 to 3 days later either by lowering the concentration of antigen to a level that does not support primary responses and providing a survival signal through transgenic Bcl-2 in vitro or simply by transferring early day 3 CTLs to antigen-free lymphoid-replete mice. In lymphoid-replete mice, established OVA-expressing E.G7 tumor was rejected by short-term CTLs that simultaneously acquired memory-like properties in secondary lymphoid tissues, where tumor antigen level remained low. Collectively, these data indicate that CTLs readily converted to memory-like cells upon lowering antigen to a concentration that selectively supports memory responses and suggest that such conversion predicts successful adoptive immunotherapy.
AB - Adoptive T-cell therapy with CD8+ CTLs is often characterized by poor persistence of the transferred T cells and limited effector responses. Improved persistence and therapeutic efficacy have been noted when antigen-activated CD8+ T cells express properties of memory cells. The current study was undertaken to more precisely characterize the development of memory-like CD8+ T cells from short-term CTLs in vitro and upon transfer in vivo, including their antitumor activity. Ovalbumin (OVA)-specific OT-I CTLs acquired phenotypic and functional properties of memory cells 2 to 3 days later either by lowering the concentration of antigen to a level that does not support primary responses and providing a survival signal through transgenic Bcl-2 in vitro or simply by transferring early day 3 CTLs to antigen-free lymphoid-replete mice. In lymphoid-replete mice, established OVA-expressing E.G7 tumor was rejected by short-term CTLs that simultaneously acquired memory-like properties in secondary lymphoid tissues, where tumor antigen level remained low. Collectively, these data indicate that CTLs readily converted to memory-like cells upon lowering antigen to a concentration that selectively supports memory responses and suggest that such conversion predicts successful adoptive immunotherapy.
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U2 - 10.1158/0008-5472.CAN-07-3040
DO - 10.1158/0008-5472.CAN-07-3040
M3 - Article
VL - 68
SP - 2984
EP - 2992
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 8
ER -