TCR gene-engineered T cell: Limited T cell activation and combined use of IL-15 and IL-21 ensure minimal differentiation and maximal antigen-specificity
被引:15
作者:
Pouw, Nadine
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机构:
Erasmus MC Daniel Den Hoed Canc Ctr, Lab Expt Tumor Immunol, Dept Med Oncol, NL-3075 EA Rotterdam, NetherlandsErasmus MC Daniel Den Hoed Canc Ctr, Lab Expt Tumor Immunol, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands
Pouw, Nadine
[1
]
Treffers-Westerlaken, Elike
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Erasmus MC Daniel Den Hoed Canc Ctr, Lab Expt Tumor Immunol, Dept Med Oncol, NL-3075 EA Rotterdam, NetherlandsErasmus MC Daniel Den Hoed Canc Ctr, Lab Expt Tumor Immunol, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands
Treffers-Westerlaken, Elike
[1
]
Mondino, Anna
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Ist San Raffaele Telethon Terapia Genica, Milan, ItalyErasmus MC Daniel Den Hoed Canc Ctr, Lab Expt Tumor Immunol, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands
Mondino, Anna
[3
]
Lamers, Cor
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Erasmus MC Daniel Den Hoed Canc Ctr, Lab Clin Tumor Immunol, Dept Med Oncol, Rotterdam, NetherlandsErasmus MC Daniel Den Hoed Canc Ctr, Lab Expt Tumor Immunol, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands
Lamers, Cor
[2
]
Debets, Reno
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Erasmus MC Daniel Den Hoed Canc Ctr, Lab Expt Tumor Immunol, Dept Med Oncol, NL-3075 EA Rotterdam, NetherlandsErasmus MC Daniel Den Hoed Canc Ctr, Lab Expt Tumor Immunol, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands
Debets, Reno
[1
]
机构:
[1] Erasmus MC Daniel Den Hoed Canc Ctr, Lab Expt Tumor Immunol, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands
[2] Erasmus MC Daniel Den Hoed Canc Ctr, Lab Clin Tumor Immunol, Dept Med Oncol, Rotterdam, Netherlands
[3] Ist San Raffaele Telethon Terapia Genica, Milan, Italy
Common-gamma cytokines;
Primary T lymphocytes;
Retroviral transduction;
T cell activation;
T cell differentiation;
TCR transgenes;
CLINICAL IMMUNOGENE THERAPY;
SUPERIOR ANTITUMOR IMMUNITY;
CANCER REGRESSION;
SINGLE-CHAIN;
RETROVIRAL TRANSDUCTION;
ADOPTIVE IMMUNOTHERAPY;
METASTATIC MELANOMA;
LYMPHOCYTES;
MEMORY;
EXPRESSION;
D O I:
10.1016/j.molimm.2010.02.022
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Clinical TCR gene therapy of melanoma represents a feasible and promising treatment rationale yet is currently challenged by objective response rates that stay behind those observed with conventional adoptive T cell therapy. Here, the phenotype and function of TCR-transduced T cells, considered to determine the efficacy of TCR gene therapy, were studied in relation to T cell activation and cytokine treatments. We observed that the lectin Concanavalin A (ConA), and to a lesser extent anti-CD3 and CD28 mAbs (soluble CD3/CD28), resulted in functional surface expression of the TCR alpha beta transgenes and enhanced fractions of CD62L(hi), CD44(lo) naive T cells. T cell functions and limited T cell differentiation were most significant when T cells were treated with a combination of IL-15 and IL-21 rather than IL-2. In comparison, anti-CD3 and CD28 mAbs coated to either latex or polystyrene beads (polystyrene or latex CD3/CD28) resulted in improved TCR expression levels and enhanced T cell differentiation irrespective of cytokine treatment, with effects most pronounced for polystyrene CD3/CD28.T cells demonstrated enhanced cytotoxic activity and IFN gamma production when activated with CD3/CD28 beads and treated with IL-15 and IL-21, but at the same time displayed non-specific T cell responses. In contrast, ConA and soluble CD3/CD28 activations resulted in antigen-specific T cell responses. In short, we show that retroviral TCR engineering of primary T cells benefits from activation with ConA or soluble CD3/CD28 rather than immobilized anti-CD3 and CD28 mAbs with respect to T cell differentiation and antigen-specificity of T cell responses. (C) 2010 Elsevier Ltd. All rights reserved.
机构:
Fred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Berger, Carolina
Jensen, Michael C.
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City Hope Natl Med Ctr, Div Canc Immunotherapeut & Tumor Immunol, Duarte, CA 91010 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Jensen, Michael C.
Lansdorp, Peter M.
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机构:
British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, CanadaFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Lansdorp, Peter M.
Gough, Mike
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h-index: 0
机构:
Univ Washington, Natl Primate Ctr, Seattle, WA 98195 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Gough, Mike
Elliott, Carole
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h-index: 0
机构:
Univ Washington, Natl Primate Ctr, Seattle, WA 98195 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Elliott, Carole
Riddell, Stanley R.
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机构:
Fred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Univ Washington, Dept Med, Seattle, WA 98195 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
机构:
Fred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Berger, Carolina
Jensen, Michael C.
论文数: 0引用数: 0
h-index: 0
机构:
City Hope Natl Med Ctr, Div Canc Immunotherapeut & Tumor Immunol, Duarte, CA 91010 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Jensen, Michael C.
Lansdorp, Peter M.
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, CanadaFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Lansdorp, Peter M.
Gough, Mike
论文数: 0引用数: 0
h-index: 0
机构:
Univ Washington, Natl Primate Ctr, Seattle, WA 98195 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Gough, Mike
Elliott, Carole
论文数: 0引用数: 0
h-index: 0
机构:
Univ Washington, Natl Primate Ctr, Seattle, WA 98195 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Elliott, Carole
Riddell, Stanley R.
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA
Univ Washington, Dept Med, Seattle, WA 98195 USAFred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA