Regulatory T Cell as Predictor of Intramyocardial Hemorrhage in STEMI Patients After Primary PCI

Background: Intramyocardial hemorrhage (IMH) is a result of ischemia-reperfusion injury in ST-segment elevation myocardial infarction(STEMI) after primary percutaneous coronary intervention (PPCI). Despite patients with IMH show poorer prognoses, studies investigating predictors of IMH occurrence are scarce. This study firstly investigated the effectiveness of regulatory T cell (Treg), peak value of Creatine Kinase MB (pCKMB), high-sensitivity C-reactive protein (hsCRP), and left ventricular end-systolic diameter (LVESD) as predictors for IMH in STEMI patients received PPCI.Methods: A prospective observational cohort study was performed in STEMI patients with cardiac magnetic resonance examination 6.3±2.3 days after PPCI. Logistic regression analysis was used to screen the risk factors for IMH. The predictive ability of risk factors for IMH were determined by Receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and C-index.Results: Of the 182 patients, 80 patients (44.0%) developed IMH. On multivariable analysis, all 4 biomarkers were independent predictors of IMH [odds radio (OR) and 95% confidence interval (CI): 0.350(0.202-0.606) for Treg, 1.004(1.001-1.006) for pCKMB, 1.060(1.022-1.100) for hsCRP, and 3.329(1.346-8.236) for LVESD]. After propensity score matching, the biomarkers individually and together significantly predicted IMH with areas under the curve of 0.750 for Treg, 0.721 for pCKMB, 0.656 for hsCRP, 0.633 for LVESD, and 0.821 for the integrated 4-marker panel. The addition of integrated 4-marker panel to a baseline risk model had an incremental effect on the predictive value for IMH [NRI: 0.197 (0.039 to 0.356); IDI: 0.200 (0.142 to 0.259); C-index: 0.806 (0.744 to 0.869), all p < 0.05].Conclusions: Treg individually or in combination with pCKMB, hsCRP, and LVESD can effectively predict the existence of IMH in STEMI patients received PPCI.Name of the registry: ClinicalTrials. govTrial registration number: NCT03939338Date of registration: 6 May 2019URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03939338?term=03939338&cntry=CN&draw=2&rank=1

Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience

We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020). Data on patient characteristics, manufacturing parameters, and manufacturing outcomes were collected from manufacturing batch records and entered into a secure database. Overall, 88% (36/41) of PolyTreg products met release criteria and 83% (34/41) of products were successfully infused into patients. Of the 7 not infused, 5 failed release criteria, and 2 were not infused because the patient became ineligible due to a change in clinical status. The median fold expansion over the 14-day manufacturing process was 434.8 -fold (range 29.8-2,232), resulting in a median post-expansion cell count of 1,841 x 106 (range 56.9-16,179 x 106). The main correlate of post-expansion cell number was starting cell number, which positively correlates with absolute circulating Treg cell count. Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production.