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Differential gene expression profile of first-generation and second-generation rapamycin-resistant allogeneic T cells.

ABSTRACT: BACKGROUND AIMS:We completed a phase II clinical trial evaluating rapamycin-resistant allogeneic T cells (T-rapa) and now have evaluated a T-rapa product manufactured in 6 days (T-rapa(6)) rather than 12 days (T-Rapa(12)). METHODS:Using gene expression microarrays, we addressed our hypothesis that the two products would express a similar phenotype. The products had similar phenotypes using conventional comparison methods of cytokine secretion and surface markers. RESULTS:Unsupervised analysis of 34,340 genes revealed that T-rapa(6) and T-rapa(12) products clustered together, distinct from culture input CD4(+) T cells. Statistical analysis of T-rapa(6) products revealed differential expression of 19.3% of genes (n = 6641) compared with input CD4(+) cells; similarly, 17.8% of genes (n = 6147) were differentially expressed between T-rapa(12) products and input CD4(+) cells. Compared with input CD4(+) cells, T-rapa(6) and T-rapa(12) products were similar in terms of up-regulation of major gene families (cell cycle, stress response, glucose catabolism, DNA metabolism) and down-regulation (inflammatory response, immune response, apoptosis, transcriptional regulation). However, when directly compared, T-rapa(6) and T-rapa(12) products showed differential expression of 5.8% of genes (n = 1994; T-rapa(6) vs. T-rapa(12)). CONCLUSIONS:Second-generation T-rapa(6) cells possess a similar yet distinct gene expression profile relative to first-generation T-rapa(12) cells and may mediate differential effects after adoptive transfer.

SUBMITTER: Castiello L

PROVIDER: S-EPMC4148082 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Differential gene expression profile of first-generation and second-generation rapamycin-resistant allogeneic T cells.

Castiello Luciano L Mossoba Miriam M Viterbo Antonella A Sabatino Marianna M Fellowes Vicki V Foley Jason E JE Winterton Matthew M Halverson David C DC Civini Sara S Jin Ping P Fowler Daniel H DH Stroncek David F DF

Cytotherapy 20130124 5

<h4>Background aims</h4>We completed a phase II clinical trial evaluating rapamycin-resistant allogeneic T cells (T-rapa) and now have evaluated a T-rapa product manufactured in 6 days (T-rapa(6)) rather than 12 days (T-Rapa(12)).<h4>Methods</h4>Using gene expression microarrays, we addressed our hypothesis that the two products would express a similar phenotype. The products had similar phenotypes using conventional comparison methods of cytokine secretion and surface markers.<h4>Results</h4>Un ...[more]

PMID: 23352462

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Project description:BackgroundThere is a paucity of data regarding the long-term clinical outcomes of first- versus second-generation drug-eluting stent (DES), especially when used to treat complex lesions such as bifurcation lesions.ObjectivesThe current study compares the efficacy and safety of first- versus second-generation DES at the 5-year follow-up in patients who underwent bifurcation percutaneous coronary intervention (PCI).MethodsA total of 5,498 patients with a bifurcation lesion who underwent PCI were pooled at a single patient level from COBIS (Coronary Bifurcation Stenting) registries II and III. Five-year target lesion failure (TLF) (the composite of cardiac death, myocardial infarction [MI], and target lesion revascularization [TLR]) and cardiac death or MI were compared between the use of first-generation DES (n = 2,436) and second-generation DES (n = 3,062) during PCI. Propensity score matching was performed to reduce selection bias.ResultsAfter a 1:1 propensity score matching procedure was conducted, the cohort consisted of 1,702 matched pairs. Patients treated with second-generation DES had a significantly lower risk of TLF at 5 years than those treated with first-generation DES in both overall and propensity-matched populations (matched hazard ratio [HRmatched]: 0.576; 95% confidence interval [CI]: 0.456 to 0.727; p <0.001). There were no significant differences in risk of a composite of cardiac death or MI between the 2 groups (HRmatched: 0.782; 95% CI: 0.539 to 1.133, P = 0.193). However, among patients who required a 2-stent technique, use of the second-generation DES reduced cardiac death or MI (HRmatched:0.422; 95% CI: 0.209 to 0.851, P = 0.016). On the other hand, among patients who required a one-stent technique, the risk of a composite of cardiac death or MI was similar between the 2 groups (HRmatched: 1.046; 95% CI: 0.664 to 1.650, P = 0.845). There was a significant interaction between stent generation and treatment strategy for cardiac death or MI (interaction P = 0.029).ConclusionsIn patients treated with PCI for a bifurcation lesion, the use of second-generation DES was associated with a significantly reduced risk of 5-year TLF than the use of first-generation DES. (Korean Coronary Bifurcation Stenting Registry II [NCT01642992]; COBIS II) (Korean Coronary Bifurcation Stenting Registry III [NCT03068494] COBIS III).

Dataset Information

Differential gene expression profile of first-generation and second-generation rapamycin-resistant allogeneic T cells.

Publications

Differential gene expression profile of first-generation and second-generation rapamycin-resistant allogeneic T cells.

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