Description
Applications
The CliniMACS CD34 Product Line was developed for the enrichment of CD34+ cells from human heterogeneous hematologic cell populations in combination with the CliniMACS System.
Referenced literature
CD34 enrichment of hematopoietic progenitor cells (HPC) is performed to provide an allogeneic stem cell graft highly purified for CD34+ cells and depleted of unwanted cells.
Highly purified CD34+ enriched stem cell grafts were reportedly used for HLA mismatched (MMUD/MMRD) and haploidentical hematopoietic stem cell transplantations (haplo-HSCT)1-3, as well as for HLA identical sibling (MRD) and matched unrelated donor (MUD) cell transplantations4–7. To overcome poor graft function (PGF) after HSCT CD34+ selected stem cell boosts (SCB) were utilized in pediatrics and adults8–11. T cell depletion (TCD) facilitated by CD34+ cell enrichment is also described in combination with reduced intensity conditioning (RIC)12 and umbilical cord blood transplantation13,14. In addition outcomes of TCD in both malignant1,4,6 and non-malignant diseases have been published7,15. Different methods of graft manipulation and future prospects of ex vivo TCD in allogeneic HSCT have been reviewed27.
In autologous transplantation CD34+ progenitor cells can be enriched in order to passively remove tumor cells from the graft (tumor cell purging)16,17. Enriched CD34+ cells have also been used to deplete auto-reactive cells from stem cell grafts for refractory autoimmune diseases, such as multiple sclerosis, severe scleroderma, systemic lupus erythematosus, and systemic sclerosis18-22. Genetically engineered hematopoietic stem cells for clinical gene therapy have been studied for over a decade and early limitations have been addressed23. The first ex vivo stem cell gene therapy for patients with ADA-SCID are commercially available autologous CD34+ enriched cells transduced to express adenosine deaminase24-26.
Disclaimer
The CliniMACS® System components, including Reagents, Tubing Sets, Instruments, and PBS/EDTA Buffer, are designed, manufactured and tested under a quality system certified to ISO 13485.
In the EU, the CliniMACS System components are available as CE-marked medical devices for their respective intended use, unless otherwise stated. The CliniMACS Reagents and Biotin Conjugates are intended for in vitro use only and are not designated for therapeutic use or direct infusion into patients. The CliniMACS Reagents in combination with the CliniMACS System are intended to separate human cells. Miltenyi Biotec as the manufacturer of the CliniMACS System does not give any recommendations regarding the use of separated cells for therapeutic purposes and does not make any claims regarding a clinical benefit. For the manufacturing and use of target cells in humans the national legislation and regulations - e.g., for the EU the Directive 2004/23/EC ("human tissues and cells"), or the Directive 2002/98/EC ("human blood and blood components") - must be followed. Thus, any clinical application of the target cells is exclusively within the responsibility of the user of a CliniMACS System.
In the US, the CliniMACS CD34 Reagent System, including the CliniMACS Plus Instrument, CliniMACS CD34 Reagent, CliniMACS Tubing Sets TS and LS, and the CliniMACS PBS/EDTA Buffer, is FDA approved as a Humanitarian Use Device (HUD), authorized by U.S. Federal law for use in the treatment of patients with acute myeloid leukemia (AML) in first complete remission. The effectiveness of the device for this indication has not been demonstrated. Other products of the CliniMACS Product Line are available for use only under an approved Investigational New Drug (IND) application, Investigational Device Exemption (IDE) or FDA approval.
CR/GMP products are for ex vivo cell processing only, and are not intended for human in vivo applications. CR/GMP products are designed, manufactured and tested under an ISO 13485 quality management system and are in compliance with relevant GMP guidelines. They are designed following the recommendations of USP <1043> on ancillary materials. The manufacturing and testing of CR/GMP products of biological origin are in compliance with EP chapter 5.2.12 for “Raw materials of biological origin for the production of cell-based and gene therapy medicinal products”.
In Canada, any clinical application of the output product must be performed in accordance with applicable Canadian legislation and regulations that pertain to cellular therapies (e.g. for advanced cellular therapies, the applicable sections of the Food and Drugs Act and the Food and Drug Regulations).
Overview
The CD34 antigen is a single transmembrane glycoprotein that is mainly expressed on human hematopoietic stem and progenitor cells but is also present on endothelial progenitor cells.
The CD34 antigen is involved in cell adhesion and is thought to function as a signaling molecule.
The CliniMACS® CD34 Product Line consists of murine anti-CD34 monoclonal antibodies conjugated to superparamagnetic iron dextran particles.
One vial contains 7.5 mL sterile, non-pyrogenic solution.
The performance of the CliniMACS CD34 Product Line depends on the individual separation strategy. For information on respective capacities, refer to the CliniMACS User Manual or contact your local representative.
Please inquire about required CliniMACS System components and accessories.
