Viable CD34 cell count of the graft is both accurate and precise when measured on a separate sample frozen together with the cord blood unit. This measurement can be performed by the transplant center to exclude between-laboratory variability.
Background—
Bone marrow CD133-postive (CD133
+
) cells possess high hematopoietic and angiogenic capacity. We tested the feasibility, safety, and functional effects of the use of enriched CD133
+
progenitor cells after intracoronary administration in patients with recent myocardial infarction.
Methods and Results—
Among 35 patients with acute myocardial infarction treated with stenting, 19 underwent intracoronary administration of CD133
+
progenitor cells (12.6±2.2×10
6
cells) 11.6±1.4 days later (group 1) and 16 did not (group 2). At 4 months, left ventricular ejection fraction increased significantly in group 1 (from 45.0±2.6% to 52.1±3.5%,
P
<0.05), but only tended to increase in case-matched group 2 patients (from 44.3±3.1% to 48.6±3.6%,
P
=NS). Likewise, left ventricular regional chordae shortening increased in group 1 (from 11.5±1.0% to 16.1±1.3%,
P
<0.05) but remained unchanged in group 2 patients (from 11.1±1.1% to 12.7±1.3%,
P
=NS). This was paralleled by reduction in the perfusion defect in group 1 (from 28.0±4.1% to 22.5±4.1%,
P
<0.05) and no change in group 2 (from 25.0±3.0% to 22.6±4.1%,
P
=NS). In group 1, two patients developed in-stent reocclusion, 7 developed in-stent restenosis, and 2 developed significant de novo lesion of the infarct-related artery. In group 2, four patients showed in-stent restenosis. In group 1 patients without reocclusion, glucose uptake shown by positron emission tomography with
18
fluorodeoxyglucose in the infarct-related territory increased from 51.2±2.6% to 57.5±3.5% (
P
<0.05). No stem cell-related arrhythmias were noted, either clinically or during programmed stimulation studies at 4 months.
Conclusion—
In patients with recent myocardial infarction, intracoronary administration of enriched CD133
+
cells is feasible but was associated with increased incidence of coronary events. Nevertheless, it seems to be associated with improved left ventricular performance paralleled with increased myocardial perfusion and viability.
Messenger RNA (mRNA) has become a promising tool in therapeutic cancer vaccine strategies. Owing to its flexible design and rapid production, mRNA is an attractive antigen delivery format for cancer vaccines targeting mutated peptides expressed in a tumor-the so-called neoantigens. These neoantigens are rarely shared between patients, and inclusion of these antigens in a vaccine requires the production of individual batches of patient-tailored mRNA. The authors have developed MIDRIX NEO , a personalized mRNA-loaded dendritic cell vaccine targeting tumor neoantigens, which is currently being evaluated in a phase 1 clinical study in lung cancer patients. To facilitate this study, the authors set up a Good Manufacturing Practice (GMP)-compliant production process for the manufacture of small batches of personalized neoantigenencoding mRNA. In this article, the authors describe the complete mRNA production process and the extensive quality assessment to which the mRNA is subjected. Validation runs have shown that the process delivers mRNA of reproducible, high quality. This process is now successfully applied for the production of neoantigen-encoding mRNA for the clinical evaluation of MIDRIX NEO . To the authors' knowledge, this is the first time that a GMP-based production process of patient-tailored neoantigen mRNA has been described.
Vandekerckhove (2020): Treatment of a patient with severe cytomegalovirus (CMV) infection after haploidentical stem cell transplantation with donor-derived CMV-specific T cells, Acta Clinica Belgica,
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