Optimization of Leukocyte Collection and Monocyte Isolation for Dendritic Cell Culture

Strasser, Erwin; Eckstein, Reinhold

doi:10.1016/j.tmrv.2009.11.004

Cited by 37 publications

(30 citation statements)

References 77 publications

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“…The conditions used for generation of the DCs from elutriated monocytes efficiently produced cells with the desired phenotype, typical of mature DCs (46). Migration of DCs is highly dependent upon their state of maturation, with mature DCs showing superior migratory capacity in comparison to immature DCs (36).…”

Section: Discussionmentioning

confidence: 99%

Tn-MUC1 DC Vaccination of Rhesus Macaques and a Phase I/II Trial in Patients with Nonmetastatic Castrate-Resistant Prostate Cancer

Scheid

Major

Bergeron

et al. 2016

Cancer Immunology Research

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MUC1 is a glycoprotein expressed on the apical surface of ductal epithelial cells. Malignant transformation results in loss of polarization and overexpression of hypoglycosylated MUC1 carrying truncated carbohydrates known as T or Tn tumor antigens. Tumor MUC1 bearing Tn carbohydrates (Tn-MUC1) represent a potential target for immunotherapy. We evaluated the Tn-MUC1 glycopeptide in a human phase I/II clinical trial for safety that followed a preclinical study of different glycosylation forms of MUC1 in rhesus macaques, whose MUC1 is highly homologous to human MUC1. Either unglycosylated rhesus macaque MUC1 peptide (rmMUC1) or Tn-rmMUC1 glycopeptide were mixed with an adjuvant, or loaded on autologous dendritic cells (DCs), and responses compared. Unglycosylated rmMUC1 peptide induced negligible humoral or cellular responses compared to the Tn-rmMUC1 glycopeptide. Tn-rmMUC1 loaded on DCs induced the highest anti-rmMUC1 T-cell responses and no clinical toxicity. In the phase I/II clinical study, 17 patients with non-metastatic castrate-resistant prostate cancer (nmCRPC) were tested with aTn-MUC1 glycopeptide-DC vaccine. Patients were treated with multiple intradermal and intranodal doses of autologous DCs, which were loaded with the Tn-MUC1 glycopeptide (and KLH as a positive control for immune reactivity). PSA doubling time (PSADT) improved significantly in 11 of 16 evaluable patients (P = 0.037). Immune response analyses detected significant Tn-MUC1-specific CD4+ and/or CD8+ T-cell intracellular cytokine responses in 5 out of 7 patients evaluated. In conclusion, vaccination with Tn-MUC1-loaded DCs in nmCRPC patients appears to be safe, able to induce significant T-cell responses, and have biological activity as measured by the increase in PSADT following vaccination.

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Section: Discussionmentioning

confidence: 99%

Tn-MUC1 DC Vaccination of Rhesus Macaques and a Phase I/II Trial in Patients with Nonmetastatic Castrate-Resistant Prostate Cancer

Scheid

Major

Bergeron

et al. 2016

Cancer Immunology Research

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“…More recently, allogeneic hematopoietic progenitor cell (HPC) transplantation was developed, and several autologous and allogeneic cellular immunotherapy protocols are being used in different clinical settings . However, in all cases, the collection of enough cells is the first step in planning for and delivering cellular therapies to the patients and leukocytapheresis has become the method of choice for collecting the sufficient number of cells to initiate either autologous or allogeneic cellular therapy protocols, such as dendritic cell therapies, extracorporeal photopheresis (ECP), donor lymphocyte infusions, and chimeric antigen receptor (CAR) T‐cell therapy …”

Section: Introductionmentioning

confidence: 99%

Leukocytapheresis in nonmobilized donors for cellular therapy protocols: Evaluation of factors affecting collection efficiency of cells

Cid

Carbassé

Alba

et al. 2019

J of Clinical Apheresis

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Introduction Collection efficiency (CE1) of cells refers to the number of cells that are collected from the total number of cells processed by the apheresis device. Limited data are available about the CE1 of cells when performing leukocytapheresis in nonmobilized donors for cellular therapy purposes. The aim of our study was to evaluate donor‐ and procedure‐related characteristics that might influence the CE1 of cells. Material and Methods Variables that predicted the CE1 of cells were analyzed by longitudinal linear regression in a series of 1071 leukocytapheresis procedures on 249 nonmobilized donors. Donor‐related characteristics considered were gender, age, total blood volume, and complete blood count (CBC) data. Procedure‐related characteristics considered were vascular access and device used. Results Older donor age was associated with a decrease in the CE1 of leukocytes, lymphocytes, monocytes, and mononuclear cells (MNCs; sum of leukocytes and monocytes) and with an increase in the CE1 of platelets (P < .05). Preprocedure CBC data (leukocytes, lymphocytes, monocytes, and platelets) were associated with either a statistically significant increase or decrease in the CE1 of cells. Central line used as vascular access was associated with a statistically significant decrease in the CE1 of MNCs (P = .02). Conclusion Donor's age, preprocedure CBC data as well as central line used as vascular access were factors associated with CE1 of cells. Knowing these characteristics is helpful in the apheresis unit when designing cellular therapy protocols in order to maximize the CE1 of the desired cell and to personalize collection variables for each donor.

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“…While the available systems are similar, product characteristics may differ slightly depending on the approach[16]. When selecting a particular collection method for CAR-T cell production many factors must be considered including the availability of instruments, kits, reagents, and trained staff.…”

Section: Apheresis Collection For Car T Cell Therapymentioning

confidence: 99%

“…Importantly, because elutriation takes cell size into account, this method is capable of distinguishing between monocytes and lymphocytes in addition to RBC reduction. Elutriation has already been used extensively in dendritic cell vaccine production[16, 37, 38] and more recently adapted to isolate lymphocytes for T cell immunotherapy[39, 40]. Scalable, GMP-compliant, closed system elutriation instruments are commercially available (Elutra Cell Separation System, TerumoBCT Inc.).…”

Section: Cell Processing In Car-t Cell Manufacturingmentioning

confidence: 99%

CAR-T Cell Therapies From the Transfusion Medicine Perspective

Fesnak

Lin

Siegel

et al. 2016

Transfusion Medicine Reviews

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The use of chimeric antigen receptor (CAR)-T cell therapy for the treatment of hematologic malignancies has generated significant excitement over the last several years. From a transfusion medicine perspective, the implementation of CAR-T therapy as a potential mainstay treatment for not only hematologic but also solid-organ malignancies represents a significant opportunity for growth and expansion. In this review, we will describe the rationale for the development of genetically re-directed T-cells as a cancer therapeutic, the different elements that are required to engineer these cells, as well as an overview of the process by which patient cells are harvested and processed to create and subsequently validate CAR-T cells. Finally, we will briefly describe some of the toxicities and clinical efficacy of CAR-T cells in the setting of patients with advanced malignancy.

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Optimization of Leukocyte Collection and Monocyte Isolation for Dendritic Cell Culture

Cited by 37 publications

References 77 publications

Tn-MUC1 DC Vaccination of Rhesus Macaques and a Phase I/II Trial in Patients with Nonmetastatic Castrate-Resistant Prostate Cancer

Tn-MUC1 DC Vaccination of Rhesus Macaques and a Phase I/II Trial in Patients with Nonmetastatic Castrate-Resistant Prostate Cancer

Leukocytapheresis in nonmobilized donors for cellular therapy protocols: Evaluation of factors affecting collection efficiency of cells

CAR-T Cell Therapies From the Transfusion Medicine Perspective

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