Presented by Ke-Yong Shi
2012.12.16
StemEx® : from Research to
Clinical Trial
Background
Each year, approximately 60,000 patients with leukemia or lymphoma
need a bone marrow transplantation. Of these, only approximately
25,000 are transplanted, primarily because the other 35,000 are unable
to find a fully matched bone marrow donor.
Cord blood transplantation (CBT) does not require full tissue matching
and is considered a good alternative for transplantation.
CBT is limited by a low number of TNC and CD34+ cells, Ex-vivo
expansion is a strategy employed to increase the number of
stem/progenitor cells and improve clinical outcomes.
Question?
Metal ions such as Fe, Ca, Mg, and Zn are known to play important roles
in basic cell functions such as cell survival, proliferation, and
differentiation.
Cu deficiency is often associated with hematopoietic cell differentiation
arrest, which results in anemia, neutropenia, and thrombocytopenia.
the role of Cu?
Zidar BL, et al. Am J Hematol. 1977;3:177–185.
Hirase N, et al. Acta Haematol. 1992;87:195–197.
Banno S, et al. Rinsho Ketsueki. 1994;35:1276–1281.
Modulation of cellular Cu by TEPA
effect on cell proliferation
Purified CD34+ cells were
cultured in 24-well Costar
Cell Culture Clusters at 104
cells/ml in alpha medium
supplemented with 10% FBS
and the following human
recombinant cytokines: TPO,
IL-6 and FLT-3, at final
concentration of 50 ng/ml
each, and IL-3 at 20 ng/ml.
effect on cell proliferation
Other Metal Ions
effect on cell differentiation
effect on cell differentiation
Progenitor cell purification
research-grade CD34-based
separation device
clinical grade CD133-based
device.
Clinical-scale ex vivo expansion
Cultures were initiated with 1/104 cells/mL, grown in 290 mL culture bags (initial
culture volume/bag, 25 mL) in alpha medium supplemented with FCS, a combination
of four cytokines (SCF, TPO, IL-6 and FLT-3 ligand, 50 ng/mL each) and 5 mm
TEPA.
Clinical-scale ex vivo expansion
Evaluation of the expansion procedure
Evaluation of the expansion procedure
Evaluation of the expansion procedure
NOD/SCID engraftment potential of the expanded graft
NOD/SCID engraftment potential of the expanded graft
StemEx®
StemEx is a graft of stem/progenitor cells isolated and expanded from a
portion of a single unit of umbilical cord blood (CBU) and transplanted in
combination with non-expanded cells from the same unit.
The market potential of StemEx is estimated at more than one billion
USD.
StemEx is now being Phase III pivotal registration clinical trial. Safety
and efficacy clinical outcomes of the study will be available in Q4/2012.