Preclinical automated, closed-system methods for positive and negative selection of lymphohematopoietic cells have been developed in collaboration with biotechnology firms that have developed systems for potential application to clinical cellular therapies. Baxter Isolex. Over 50 preclinical evaluations were carried out with the Isolex 3005A system (Baxter Healthcare, Inc., Irvine, CA) for immunomagnetic positive selection of CD34+ hematopoietic progenitor cells. These evaluations accomplished the requisite development and validation of this methodology before incorporating it into a clinical trial of gene therapy for chronic granulomatous disease. Current studies are focusing on development and validation of the new Isolex i, an improved, more automated version of this system. In ongoing studies of this device, we are processing granulocyte-colony stimulating factor (G-CSF)-mobilized normal donor leukapheresis collections and evaluating the yield of CD34+ cells, the depletion of CD3+ T cells, and the system's overall utility. Results of this evaluation and comparison with evaluations of other systems (see below) will determine its applicability for specific clinical trials. CellPro T Cell Depletion System (CellPro Inc., Bothell, WA). A preclinical evaluation of this two-step positive (CD34) and negative (CD2) selection system, which uses an immunoadsorption approach, was recently completed. For eight G-CSF-mobilized leukapheresis products from normal donors, mean depletion of CD3+ T cells was 3.75 logs, and mean CD34+ cell yield was 44 percent. This system is ready for incorporation into clinical trials of allogeneic T-depleted hematopoietic transplantation after required regulatory applications to the Food and Drug Administration. These results will also be evaluated in relationship to those from the ongoing Baxter Isolex system evaluation described.
| 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 |
