The scale-up of T cell depletion for mismatched bone marrow transplants

Ying Xiong, Xiaodong Tong, Sherif Farag, Jeffrey Chalmers

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Graft-versus-host disease (GVHD) is the major limitation preventing allogeneic stem cell transplantation (SCT) in a clinical setting; however SCT is the only curative option, to date, for a variety of hematological malignancies. It is generally believed that GVHD can be prevented by the use of large doses of CD34+ progenitor cells in a sample which has had a significant depletion of T cells. A subset of T-cells mediate GVHD. The number of progenitor cells necessary for safe engraftment may depend on several factors. Generally, 1×10E7 CD34+ progenitor cells/kg body weight is required, while a certain threshold of less than 2×10e5 T-cells (CD3+)/kg body weight renders the patients at increased risk for graft rejection/failure. This level of performance standards for a typical clinical transplantation requires approximately 0.5 to 1 × 10E10 peripheral blood leukocytes (PBLs) to be processed with a 80-90% recovery of the stem cells and a 4 to 5 log 10 depletion of the T-cells. There are a number of technologies used with respect to T cell depletion and stem cell enrichment, the most efficient of which is immunomagnetic separation. Immunomagnetic separation is a promising technology using magnetism to purify cells and biological compounds. The most popular system employed for immunomagnetic cell separation that can select CD34+ cells positively is the commercial, batch MACS system. While promising, significant limitations exit with this system. A high-throughput, continuous immunomagnetic cell sorting system, Quadrupole Magnetic Cell Sorter, QMS, is being developed in our lab for a number applications including T cell depletion. We have demonstrated on small samples of human blood a (n-16) 4 log 10 T cell depletion and a 60% recovery of CD34+ cells after the separation of 10E7 PBLs. At present the research, supported by the National Cancer Institute, is focused on scaling up to be able to process on the order of 2, e108 PBLs from one buffy in an economical manner. This requires several studies to be conduced simultaneously, namley 1) Optimizing the immunomagnetic labeling of T cells, 2) Optimizing the separation of the labeled T cells in QMS, 3) Improving the models of the separation process. This presentation will present the current standing of this process.

Original languageEnglish
Title of host publicationAIChE Annual Meeting, Conference Proceedings
Pages9145
Number of pages1
StatePublished - 2005
Externally publishedYes
Event05AIChE: 2005 AIChE Annual Meeting and Fall Showcase - Cincinnati, OH, United States
Duration: Oct 30 2005Nov 4 2005

Other

Other05AIChE: 2005 AIChE Annual Meeting and Fall Showcase
CountryUnited States
CityCincinnati, OH
Period10/30/0511/4/05

Fingerprint

Transplants
T-cells
Bone
Stem cells
Grafts
Blood
Recovery
Magnetism
Sorting
Labeling
Cells
Throughput

ASJC Scopus subject areas

  • Engineering(all)

Cite this

Xiong, Y., Tong, X., Farag, S., & Chalmers, J. (2005). The scale-up of T cell depletion for mismatched bone marrow transplants. In AIChE Annual Meeting, Conference Proceedings (pp. 9145)

The scale-up of T cell depletion for mismatched bone marrow transplants. / Xiong, Ying; Tong, Xiaodong; Farag, Sherif; Chalmers, Jeffrey.

AIChE Annual Meeting, Conference Proceedings. 2005. p. 9145.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Xiong, Y, Tong, X, Farag, S & Chalmers, J 2005, The scale-up of T cell depletion for mismatched bone marrow transplants. in AIChE Annual Meeting, Conference Proceedings. pp. 9145, 05AIChE: 2005 AIChE Annual Meeting and Fall Showcase, Cincinnati, OH, United States, 10/30/05.
Xiong Y, Tong X, Farag S, Chalmers J. The scale-up of T cell depletion for mismatched bone marrow transplants. In AIChE Annual Meeting, Conference Proceedings. 2005. p. 9145
Xiong, Ying ; Tong, Xiaodong ; Farag, Sherif ; Chalmers, Jeffrey. / The scale-up of T cell depletion for mismatched bone marrow transplants. AIChE Annual Meeting, Conference Proceedings. 2005. pp. 9145
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