110 In-depth characterization of variability in apheresis collections from normal donor populations for allogeneic cell therapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A122-A122
Author(s):  
Shawn Fahl ◽  
Shawn Fahl ◽  
Shawn Fahl
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Immune Cell ◽  
Patient Specific ◽  
Normal Donor ◽  
Donor Pool ◽  
Activation Markers ◽  
Allogeneic Cell ◽  
Allogeneic Cell Therapy

BackgroundThe success of autologous CAR-T cell therapies has revolutionized and accelerated development in the cell therapy field. However, the requirement for patient-specific starting material for these therapies remains an impediment to establishing availability for all patients who could benefit, highlighting the need for a highly characterized normal donor pool to generate allogeneic cell therapy material.MethodsWe have established a network of >2800 normal donors that have been genotyped at the HLA loci (6 digits) and stratified by reactivity to common human viruses, such as cytomegalovirus (CMV) and Epstein Barr Virus (EBV). Furthermore, cell collections from 35 randomly selected donors have been screened by flow cytometry for major immune cell subsets, including T cells, B cells, NK cells, and monocytes. The T cell compartment was further characterized by expression of activation markers (CD25, PD1, CD69) and proliferative capacity in response to anti-CD3/CD28 stimulation.ResultsN/AAbstract 110 Table 1ConclusionsThere was substantial variability (%CV 14.52%-50.58%, see table 1) in the percentage of each immune cell population across the donor pool, which would have effects on the relative success of downstream cell manufacturing. We are evaluating additional donors to identify specific sources of variability. Collectively, these data highlight the need for in-depth genotypic and phenotypic characterization of donor populations to ensure that the most robust material is selected for each type of cell therapy manufacturing.

scholarly journals Safety and Efficacy of Allogeneic Cell Therapy in Infarcted Rats Transplanted With Mismatched Cardiosphere-Derived Cells

Circulation ◽  
2012 ◽  
Vol 125 (1) ◽  
pp. 100-112 ◽  
Author(s):  
Konstantinos Malliaras ◽  
Tao-Sheng Li ◽  
Daniel Luthringer ◽  
John Terrovitis ◽  
Ke Cheng ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Safety And Efficacy ◽  
Allogeneic Cell ◽  
Allogeneic Cell Therapy

Similar effect of autologous and allogeneic cell therapy for ischemic heart disease: results from a meta-analysis of large animal studies

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P1462-P1462
Author(s):  
S. J. Jansen Of Lorkeers ◽  
J. E. C. Eding ◽  
T. I. G. Van Der Spoel ◽  
H. M. Vesterinen ◽  
S. Koudstaal ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cell Therapy ◽  
Ischemic Heart Disease ◽  
Animal Studies ◽  
Meta Analysis ◽  
Ischemic Heart ◽  
Large Animal ◽  
Allogeneic Cell ◽  
Allogeneic Cell Therapy

Abstract WP338: Combined Coiling and Allogeneic Mesenchymal Stem/Stromal Cell Therapy Could be a More Cost-effective Alternative to Coiling Alone

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Amin Adibi ◽  
Arindom Sen ◽  
Alim P Mitha
Keyword(s):  
Sensitivity Analysis ◽  
Cell Therapy ◽  
Markov Model ◽  
Cost Effective ◽  
Effective Alternative ◽  
Sensitivity Testing ◽  
Allogeneic Cell ◽  
Allogeneic Cell Therapy ◽  
Cost Effective Treatment ◽  
Cost Effective Alternative

Introduction: Recurrence of intracranial aneurysms following endovascular therapy in 20% of patients remains the only major disadvantage of this treatment. For this reason, a significant amount of research has been carried out, focused on reducing the incidence of recurrence. In recent years, a variety of cell therapy modalities using fibroblasts, smooth muscle cells, endothelial progenitor cells and Mesenchymal Stem/Stromal Cells (MSCs) have been tested in animal models as a means to improve the outcome of the treatment. However, it remains unclear whether preventing recurrence using cell therapy is a more cost-effective alternative to retreating recanalized aneurysms. In this study, we have used a Markov model approach to determine efficacy thresholds at which combined coiling and cell therapy becomes a more cost-effective treatment than coiling alone. Hypothesis: Combined coiling and cell therapy will be more cost-effective than coiling alone, if it reduces the need for retreatment by 50% or more. Methods: The cell therapy was assumed to be aimed at reducing the need for retreatment. A Markov model was used to compare coiling alone with combined coiling and autologous/allogeneic cell therapy. Model inputs were mostly taken from meta-analyses. Sensitivity analysis was performed to predict efficacy thresholds that make cell therapy more cost-effective than coiling alone. Robustness of the model was assessed through further sensitivity testing focused on variables with the highest impact on the outcome. Results: Sensitivity analysis showed that coiling with autologous cell therapy becomes more cost-effective than coiling alone, if it reduces the need for retreatment by 39.9% or more. When allogeneic cell are used, a reduction of 13.3% or more in the need for retreatment is enough the make combined coiling and cell therapy more cost-effective. Conclusions: Our preliminary analysis suggests that efficacy thresholds at which combined coiling and cell therapy becomes more cost-effective than coiling alone are modest - especially for allogeneic MSC therapies. This makes combined coiling and cell therapy a viable alternative to the current standard-of-care from a cost-utility standpoint, and justifies further research and investment in the field.

FRI-155-Characterization of a library of CD4+ T cells for T-cell therapy of HBV infection

2019 ◽  
Vol 70 (1) ◽  
pp. e456
Author(s):  
Sophia Schreiber ◽  
Melanie Honz ◽  
Matthias Schiemann ◽  
Christina Zielinski ◽  
Ulrike Protzer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Cd4 T Cells ◽  
Hbv Infection ◽  
T Cell Therapy

scholarly journals Human mesenchymal stem cell sheets in xeno-free media for possible allogenic applications

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kyungsook Kim ◽  
Sophia Bou-Ghannam ◽  
Hallie Thorp ◽  
David W. Grainger ◽  
Teruo Okano
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Subcutaneous Tissue ◽  
Cell Sheet ◽  
Human Mesenchymal Stem Cell ◽  
Human Umbilical Cord ◽  
Target Tissue ◽  
Post Transplantation ◽  
Allogeneic Cell ◽  
Allogeneic Cell Therapy

Abstract Cell-based therapies are increasingly focused on allogeneic stem cell sources because of several advantages in eliminating donor variability (e.g., aging and disease pathophysiology) affecting stem cell quality and in cell-banked sourcing of healthy donors to enable “off-the-shelf” products. However, allogeneic cell therapy is limited by host patient immunologic competence and inconsistent performance due to cell delivery methods. To address allogeneic cell therapy limitations, this study developed a new allogeneic stem cell sheet using human umbilical cord mesenchymal stem cells (hUC-MSC) that present low antigenicity (i.e., major histocompatibility complex, MHC). Optimal conditions including cell density, passage number, and culture time were examined to fabricate reliable hUC-MSC sheets. MHC II antigens correlated to alloimmune rejection were barely expressed in hUC-MSC sheets compared to other comparator MSC sheets (hBMSC and hADSC). hUC-MSC sheets easily graft spontaneously onto subcutaneous tissue in immune-deficient mice within 10 minutes of placement. No sutures are required to secure sheets to tissue because sheet extracellular matrix (ECM) actively facilitates cell-target tissue adhesion. At 10 days post-transplantation, hUC-MSC sheets remain on ectopic target tissue sites and exhibit new blood vessel formation. Furthermore, implanted hUC-MSC sheets secrete human HGF continuously to the murine target tissue. hUC-MSC sheets described here should provide new insights for improving allogenic cell-based therapies.

scholarly journals Platelet Induced Functional Alteration of CD4+ and CD8+ T Cells in HNSCC

2020 ◽  
Vol 21 (20) ◽  
pp. 7507
Author(s):  
Christina Polasky ◽  
Franziska Wendt ◽  
Ralph Pries ◽  
Barbara Wollenberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Spatial Separation ◽  
Cell Regulation ◽  
Activation Markers ◽  
Indirect Contact ◽  
Cell Functions ◽  
T Cell Regulation ◽  
Regulatory Functions

Platelets (PLT) are the second most abundant cell type in human blood and exert various immune-regulatory functions under both physiological and pathological conditions. In fact, immune cell regulation via platelets has been demonstrated in several studies within the past decade. However, the exact mechanisms behind T cell regulation remain poorly understood. We questioned whether the formation of aggregates of platelets and T cells has an impact on T-cell functions. In the present study, we stimulated PBMC cultures with anti-CD3 and anti-CD28 mABs and cultured them at a PLT: PBMC ratio of 1:1 or 100:1. After 24, 48, and 72 h, PD-1, PD-L1 expression, and proliferation were analyzed on T cells using flow cytometry. Cytokine production was measured in PHA stimulated CD4 cells after 6 h. We found a significant platelet-mediated decrease in PD-1 and PD-L1 expression, proliferation, as well as IFN-γ and TNF-α production. Perturbations also at least partially remained after spatial separation of PLTs from PBMCs in Transwell-assays. T cell-platelet aggregates showed similar levels of activation markers, proliferation, and secreted cytokines as their non-complexed counterparts. Results indicate a platelet mediated regulation of T cells via direct and indirect contact, but only mediocre effects of the complex formation itself.

scholarly journals Allogeneic Cell Therapy

2015 ◽  
Vol 116 (1) ◽  
pp. 12-15 ◽  
Author(s):  
Vasileios Karantalis ◽  
Ivonne Hernandez Schulman ◽  
Wayne Balkan ◽  
Joshua M. Hare
Keyword(s):  
Cell Therapy ◽  
Allogeneic Cell ◽  
Allogeneic Cell Therapy
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