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• W2749362214 abstract "Adoptive T-cell therapy relying on conventional T cells transduced with T-cell receptors (TCRs) or chimeric antigen receptors (CARs) has caused substantial tumor regression in several clinical trials. However, genetically engineered T cells have been associated with serious side-effects due to off-target toxicities and massive cytokine release. To obviate these concerns, we established a protocol adaptable to GMP to expand and transiently transfect γ/δ T cells with mRNA. PBMC from healthy donors were stimulated using zoledronic-acid or OKT3 to expand γ/δ T cells and bulk T cells, respectively. Additionally, CD8+ T cells and γ/δ T cells were MACS-isolated from PBMC and expanded with OKT3. Next, these four populations were electroporated with RNA encoding a gp100/HLA-A2-specific TCR or a CAR specific for MCSP. Thereafter, receptor expression, antigen-specific cytokine secretion, specific cytotoxicity, and killing of the endogenous γ/δ T cell-target Daudi were analyzed. Using zoledronic-acid in average 6 million of γ/δ T cells with a purity of 85% were generated from one million PBMC. MACS-isolation and OKT3-mediated expansion of γ/δ T cells yielded approximately ten times less cells. OKT3-expanded and CD8+ MACS-isolated conventional T cells behaved correspondingly similar. All employed T cells were efficiently transfected with the TCR or the CAR. Upon respective stimulation, γ/δ T cells produced IFNγ and TNF, but little IL-2 and the zoledronic-acid expanded T cells exceeded MACS-γ/δ T cells in antigen-specific cytokine secretion. While the cytokine production of γ/δ T cells was in general lower than that of conventional T cells, specific cytotoxicity against melanoma cell lines was similar. In contrast to OKT3-expanded and MACS-CD8+ T cells, mock-electroporated γ/δ T cells also lysed tumor cells reflecting the γ/δ T cell-intrinsic anti-tumor activity. After transfection, γ/δ T cells were still able to kill MHC-deficient Daudi cells. We present a protocol adaptable to GMP for the expansion of γ/δ T cells and their subsequent RNA-transfection with tumor-specific TCRs or CARs. Given the transient receptor expression, the reduced cytokine release, and the equivalent cytotoxicity, these γ/δ T cells may represent a safer complementation to genetically engineered conventional T cells in the immunotherapy of melanoma (Exper Dermatol 26: 157, 2017, J Investig Dermatol 136: A173, 2016)." @default.
• W2749362214 created "2017-08-31" @default.
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• W2749362214 date "2017-08-17" @default.
• W2749362214 modified "2023-10-11" @default.
• W2749362214 title "RNA-transfection of γ/δ T cells with a chimeric antigen receptor or an α/β T-cell receptor: a safer alternative to genetically engineered α/β T cells for the immunotherapy of melanoma" @default.
• W2749362214 cites W1497518367 @default.
• W2749362214 cites W1504474376 @default.
• W2749362214 cites W1535243328 @default.
• W2749362214 cites W1607012924 @default.
• W2749362214 cites W1632369379 @default.
• W2749362214 cites W1782844421 @default.
• W2749362214 cites W1806806621 @default.
• W2749362214 cites W1887703508 @default.
• W2749362214 cites W1895112532 @default.
• W2749362214 cites W1904657502 @default.
• W2749362214 cites W1966280949 @default.
• W2749362214 cites W1967358904 @default.
• W2749362214 cites W1968529445 @default.
• W2749362214 cites W1972025951 @default.
• W2749362214 cites W1972297696 @default.
• W2749362214 cites W1972700907 @default.
• W2749362214 cites W1977629656 @default.
• W2749362214 cites W1978029914 @default.
• W2749362214 cites W1978076091 @default.
• W2749362214 cites W1981291019 @default.
• W2749362214 cites W1983143892 @default.
• W2749362214 cites W2007753570 @default.
• W2749362214 cites W2020312840 @default.
• W2749362214 cites W2020728494 @default.
• W2749362214 cites W2021032653 @default.
• W2749362214 cites W2022072812 @default.
• W2749362214 cites W2022330759 @default.
• W2749362214 cites W2024970157 @default.
• W2749362214 cites W2025949442 @default.
• W2749362214 cites W2043612975 @default.
• W2749362214 cites W2046488997 @default.
• W2749362214 cites W2049681631 @default.
• W2749362214 cites W2060961974 @default.
• W2749362214 cites W2072784690 @default.
• W2749362214 cites W2073245859 @default.
• W2749362214 cites W2075574520 @default.
• W2749362214 cites W2077073060 @default.
• W2749362214 cites W2083071223 @default.
• W2749362214 cites W2083153683 @default.
• W2749362214 cites W2083601518 @default.
• W2749362214 cites W2085060041 @default.
• W2749362214 cites W2087279615 @default.
• W2749362214 cites W2087986967 @default.
• W2749362214 cites W2088927226 @default.
• W2749362214 cites W2089484373 @default.
• W2749362214 cites W2091567572 @default.
• W2749362214 cites W2091954193 @default.
• W2749362214 cites W2094945699 @default.
• W2749362214 cites W2095106782 @default.
• W2749362214 cites W2098249455 @default.
• W2749362214 cites W2098839188 @default.
• W2749362214 cites W2100234690 @default.
• W2749362214 cites W2103852933 @default.
• W2749362214 cites W2105400883 @default.
• W2749362214 cites W2105879190 @default.
• W2749362214 cites W2106544491 @default.
• W2749362214 cites W2107564997 @default.
• W2749362214 cites W2110459096 @default.
• W2749362214 cites W2115176597 @default.
• W2749362214 cites W2115278843 @default.
• W2749362214 cites W2117108378 @default.
• W2749362214 cites W2119497696 @default.
• W2749362214 cites W2120490293 @default.
• W2749362214 cites W2120520998 @default.
• W2749362214 cites W2133298966 @default.
• W2749362214 cites W2136100686 @default.
• W2749362214 cites W2139399500 @default.
• W2749362214 cites W2143626441 @default.
• W2749362214 cites W2147345889 @default.
• W2749362214 cites W2150032631 @default.
• W2749362214 cites W2151246207 @default.
• W2749362214 cites W2155035972 @default.
• W2749362214 cites W2158899629 @default.
• W2749362214 cites W2159276395 @default.
• W2749362214 cites W2167553852 @default.
• W2749362214 cites W2168412386 @default.
• W2749362214 cites W2170263258 @default.
• W2749362214 cites W2262661769 @default.
• W2749362214 cites W2289064841 @default.
• W2749362214 cites W2340862784 @default.
• W2749362214 cites W2407955638 @default.
• W2749362214 cites W2410166620 @default.
• W2749362214 cites W2567365345 @default.
• W2749362214 cites W94692950 @default.
• W2749362214 doi "https://doi.org/10.1186/s12885-017-3539-3" @default.

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