POSITIVE SELECTION OF HEMATOPOIETIC CD34(-CELLS PROVIDES INDIRECT PURGING OF CD34(-) LYMPHOID-CELLS AND THE PURGING EFFICIENCY IS INCREASEDBY ANTI-CD2 AND ANTI-CD30 IMMUNOTOXINS() STEM)
Rm. Lemoli et al., POSITIVE SELECTION OF HEMATOPOIETIC CD34(-CELLS PROVIDES INDIRECT PURGING OF CD34(-) LYMPHOID-CELLS AND THE PURGING EFFICIENCY IS INCREASEDBY ANTI-CD2 AND ANTI-CD30 IMMUNOTOXINS() STEM), Bone marrow transplantation, 13(4), 1994, pp. 465-471
Human CD34(+) hematopoietic cells were purified using the avidin-bioti
n immunoabsorption technique. The selected population showed 78.6 +/-
3% CD34(+) cells and the overall recovery of CD34(+) cells, CFU-GM and
BFU-E from the starting population was 34 +/- 5%, 71 +/- 4% and 67 +/
- 2% respectively. Hematopoietic progenitor cell purification also res
ulted in 3 log of normal T cell depletion from the bone marrow (BM) by
immunofluorescence analysis. Moreover, when unseparated BM cells were
mixed with the CD34(-) lymphoma cell lines D430B and Raji, the remova
l of greater than 3 log of tumor cells from the enriched CD34(+) cell
fraction was demonstrated. To increase the neoplastic cell purging, se
veral immunotoxins (IT) containing the ribosome-inactivating protein (
RIP) saporin and directed toward the lymphoid-associated antigens CD30
and CD2 were prepared. Our experiments showed only a minimal toxicity
of the immunoconjugates on colony-forming cells (CFC) derived from pu
rified CD34(+) cells. Conversely, all the ITs were very effective in i
nhibiting protein synthesis and growth of normal and neoplastic lympho
id cells. Further experiments demonstrated that the sequential combina
tion of CD34(+) cells purification and IT treatment resulted in 5 or m
ore log of tumor cell purging with no additional loss of BM progenitor
cells.