Positive selection of hematopoietic CD34+ stem cells provides 'indirect purging' of CD34- lymphoid cells and the purging efficiency is increased by anti-CD2 and anti-CD30 immunotoxins
| Autor: | Lemoli, R. M., Tazzari, P. L., Fortuna, A., Andrea Bolognesi, Gulati, S. C., Stirpe, F., Tura, S. |
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| Rok vydání: | 1994 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Cytotoxicity Immunologic Immunotoxins Bone Marrow Purging CD2 Antigens Ki-1 Antigen Antigens CD34 Cell Separation Hematopoietic Stem Cells Lymphocyte Activation Saporins Antigens CD Protein Biosynthesis Ribosome Inactivating Proteins Type 1 Humans Receptors Immunologic N-Glycosyl Hydrolases Immunosorbent Techniques Plant Proteins |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0268-3369 |
| Popis: | Human CD34+ hematopoietic cells were purified using the avidin-biotin 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 resulted 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 removal of greater than 3 log of tumor cells from the enriched CD34+ cell fraction was demonstrated. To increase the neoplastic cell purging, several 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 purified CD34+ cells. Conversely, all the ITs were very effective in inhibiting protein synthesis and growth of normal and neoplastic lymphoid cells. Further experiments demonstrated that the sequential combination of CD34+ cells purification and IT treatment resulted in 5 or more log of tumor cell purging with no additional loss of BM progenitor cells. |
| Databáze: | OpenAIRE |
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