Preclinical and clinical studies of automated closed systems for positive and negative selection of lymphohematopoietic cells have been done in collaboration with biotechnology firms which have developed systems for potential application to clinical cellular therapies: oCellPro T-cell Depletion System: A clinical evaluation of this two-step positive (CD34) and negative (CD2) selection system, which uses an immunoabsorption approach, was completed in August 1998. This study randomized 24 allogeneic donors to fresh versus pooled processing of stem cell apheresis products. Results demonstrated equivalence between the two study arms in processing and clinical outcomes, so the pooled processing approach was used for practical and economic reasons (less processing time, lower costs associated with use of one expensive system versus two). This system is no longer clinically available. A manuscript is in preparation. oNexell, Inc. Isolex: Studies of the automated Isolex 300i for immunomagnetic selection of hematopoietic progenitor cells were continued. Over 100 selection procedures on version 2.0 (either positive only or combined positive/negative selection) have been completed, and over 25 selection procedures on version 2.5 were completed in this fiscal year. Studies of combined positive + negative selection aimed to achieve maximum T-cell depletion of peripheral blood stem cell products have led to incorporation of this method into several allogeneic transplantation protocols. Current results on the version 2.5 combined positive/negative procedure show a mean CD3+ T-cell depletion of 5 logs, with mean CD34+ cell recovery of 60 percent. Evaluation of different T-cell antibodies (CD2 alone vs. CD4+CD8 vs. CD2+CD6+CD7) demonstrated equivalence in the combined positive/negative method. A manuscript is in preparation. This method will continue to be used in clinical trials. oMiltenyi CliniMacs: In mid-FY 2000, we began a preclinical evaluation of the CliniMacs immunomagnetic selection system. Preliminary results (eight runs to date) with positive selection of normal donor mobilized PBSC show a mean CD34+ cell recovery of 55 percent and a mean CD3+ cell depletion of 5 logs. Further studies will demonstrate the utility of this system for clinical trials.
| Nakamura, R; Bahceci, E; Read, E J et al. (2001) Transplant dose of CD34(+) and CD3(+) cells predicts outcome in patients with haematological malignancies undergoing T cell-depleted peripheral blood stem cell transplants with delayed donor lymphocyte add-back. Br J Haematol 115:95-104 |
| Bahceci, E; Read, E J; Leitman, S et al. (2000) CD34+ cell dose predicts relapse and survival after T-cell-depleted HLA-identical haematopoietic stem cell transplantation (HSCT) for haematological malignancies. Br J Haematol 108:408-14 |
