Manufacturing development and clinical production of NKG2D chimeric antigen receptor-expressing T cells for autologous adoptive cell therapy.
Manufacturing development and clinical production of NKG2D chimeric antigen receptor-expressing T cells for autologous adoptive cell therapy.
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NKG2D嵌合抗原受体T细胞的生产开发和临床生产，用于自体产科疗法。
DOI：
10.1016/j.jcyt.2018.05.001
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发表时间：
2018-07
期刊：
影响因子：
4.5
通讯作者：
Nikiforow S
中科院分区：
文献类型：
--
作者：
Murad JM;Baumeister SH;Werner L;Daley H;Trébéden-Negre H;Reder J;Sentman CL;Gilham D;Lehmann F;Snykers S;Sentman ML;Wade T;Schmucker A;Fanger MW;Dranoff G;Ritz J;Nikiforow S
Adoptive cell therapy employing natural killer group 2D (NKG2D) chimeric antigen receptor (CAR)-modified T cells has demonstrated preclinical efficacy in several model systems, including hematological and solid tumors. We present comprehensive data on manufacturing development and clinical production of autologous NKG2D CAR T cells for treatment of acute myeloid leukemia and multiple myeloma (NCT02203825). An NKG2D CAR was generated by fusing native full-length human NKG2D to the human CD3ζ cytoplasmic signaling domain. NKG2D naturally associates with native costimulatory molecule DAP10, effectively generating a second-generation CAR against multiple ligands upregulated during malignant transformation including MIC-A, MIC-B and the UL-16 binding proteins. CAR T cells were infused fresh after a 9-day process wherein OKT3-activated T cells were genetically modified with replication- defective gamma-retroviral vector and expanded ex vivo for 5 days with recombinant human interleukin-2. Despite sizable interpatient variation in originally collected cells, release criteria, including T-cell expansion and purity (median 98%), T- cell transduction (median 66% CD8+ T cells), and functional activity against NKG2D ligand-positive cells, were met for 100% of healthy donors and patients enrolled and collected. There was minimal carryover of non-T cells, particularly malignant cells; both effector memory and central memory cells were generated; and inflammatory cytokines such as GM-CSF, RANTES, IFN-γ and TNFα were selectively upregulated. The process resulted in production of required cell doses for the first-in-human Phase I NKG2D CAR T clinical trial, and provides a robust, flexible base for further optimization of NKG2D CAR T-cell manufacturing.
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DOI：
10.1097/cji.0b013e318194a6e8
发表时间：
2009-02
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Hollyman D;Stefanski J;Przybylowski M;Bartido S;Borquez-Ojeda O;Taylor C;Yeh R;Capacio V;Olszewska M;Hosey J;Sadelain M;Brentjens RJ;Rivière I
通讯作者：
Rivière I
影响因子：
7.2
作者：
Spear P;Barber A;Sentman CL
通讯作者：
Sentman CL
影响因子：
5.6
作者：
Gacerez AT;Arellano B;Sentman CL
通讯作者：
Sentman CL
影响因子：
20.3
作者：
Kochenderfer, James N.;Wilson, Wyndham H.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
17.1
作者：
Thomas, Susan Napier
通讯作者：
Thomas, Susan Napier