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A combined approach for purging multidrug-resistant leukemic cell lines in bone marrow using a monoclonal antibody and chemotherapy.

Publication ,  Journal Article
Aihara, M; Aihara, Y; Schmidt-Wolf, G; Schmidt-Wolf, I; Sikic, BI; Blume, KG; Chao, NJ
Published in: Blood
May 1, 1991

Selective removal of malignant cells (purging) from bone marrow (BM) is a concern in autologous BM transplantation (ABMT). Use of vincristine, etoposide, or doxorubicin for purging could be rendered ineffective by the presence of multidrug-resistant (MDR) tumor cells. To circumvent this particular problem, we investigated whether 17F9, a monoclonal IgG2b antibody directed against the cell surface product of the MDR gene, P-glycoprotein, is effective in selective removal of MDR cells from BM when used with rabbit complement (C'). Using two different cell lines we have demonstrated that 17F9 + C' selectively lyses MDR-positive cells. Three rounds of antibody + C' resulted in 96.4% +/- 3.6% kill of K562/DOX and 100% +/- 0% of CEM/VLB cells. Mixtures of malignant cells and normal BM resulted in 99.85% removal of K562/DOX and 99.91% removal of CEM/VLB clonogenic cells. This treatment did not affect normal committed precursors compared with C' alone. The addition of the cytotoxic agent etoposide (VP-16) following antibody purging results in a 4.6 log reduction of malignant cells. Furthermore, this antibody was effective when used against patients' leukemic blasts. These results suggest the use of 17F9 + C' is effective and selective for removal of MDR cells from BM before ABMT and the addition of VP-16 enhances the purging efficacy.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

May 1, 1991

Volume

77

Issue

9

Start / End Page

2079 / 2084

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Membrane Glycoproteins
  • Leukemia
  • Immunology
  • Humans
  • Hematopoietic Stem Cells
  • Flow Cytometry
  • Etoposide
  • Drug Resistance
  • Complement System Proteins
 

Citation

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MLA
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Aihara, M., Aihara, Y., Schmidt-Wolf, G., Schmidt-Wolf, I., Sikic, B. I., Blume, K. G., & Chao, N. J. (1991). A combined approach for purging multidrug-resistant leukemic cell lines in bone marrow using a monoclonal antibody and chemotherapy. Blood, 77(9), 2079–2084.
Aihara, M., Y. Aihara, G. Schmidt-Wolf, I. Schmidt-Wolf, B. I. Sikic, K. G. Blume, and N. J. Chao. “A combined approach for purging multidrug-resistant leukemic cell lines in bone marrow using a monoclonal antibody and chemotherapy.Blood 77, no. 9 (May 1, 1991): 2079–84.
Aihara M, Aihara Y, Schmidt-Wolf G, Schmidt-Wolf I, Sikic BI, Blume KG, et al. A combined approach for purging multidrug-resistant leukemic cell lines in bone marrow using a monoclonal antibody and chemotherapy. Blood. 1991 May 1;77(9):2079–84.
Aihara M, Aihara Y, Schmidt-Wolf G, Schmidt-Wolf I, Sikic BI, Blume KG, Chao NJ. A combined approach for purging multidrug-resistant leukemic cell lines in bone marrow using a monoclonal antibody and chemotherapy. Blood. 1991 May 1;77(9):2079–2084.

Published In

Blood

ISSN

0006-4971

Publication Date

May 1, 1991

Volume

77

Issue

9

Start / End Page

2079 / 2084

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Membrane Glycoproteins
  • Leukemia
  • Immunology
  • Humans
  • Hematopoietic Stem Cells
  • Flow Cytometry
  • Etoposide
  • Drug Resistance
  • Complement System Proteins