title: Elimination of clonogenic breast cancer cells from human bone marrow. A comparison of immunotoxin treatment with chemoimmunoseparation using 4-hydroperoxycyclophosphamide, monoclonal antibodies, and magnetic microspheres.
abstract: Autologous bone marrow transplantation (ABMT) may aid in the management of breast cancer, but is currently limited to patients without bone marrow metastases. In earlier studies, 5 logs of malignant clonogenic breast cancer cells could be eliminated from human bone marrow using a combination of chemoseparation with 4-hydroperoxycyclophosphamide (4-HC) and immunoseparation with monoclonal antibodies and magnetic microspheres. In this report the authors compare chemoimmunoseparation to treatment with immunotoxins for elimination of tumor cells from human bone marrow and for the preservation of normal precursors. Breast cancer cells from each of five cell lines were mixed with a tenfold excess of irradiated human bone marrow cells. Treatment with a combination of five immunotoxins reduced clonogenic tumor cell growth by 1.8 to 5.5 logs depending upon the cell line. With two of the five cell lines, clonogenic tumor cells were eliminated quantitatively. Using the CAMA-1 breast cancer cell line, treatment with multiple immunotoxins was compared with chemoimmunoseparation with 4-HC, a panel of five unconjugated monoclonal antibodies and magnetic microspheres. Chemoimmunoseparation eliminated 3.5 to 5.4 logs of malignant cells, while preserving 21% of Colony-forming unit-granulocyte-macrophage (CFU-GM) and 37% of burst-forming unit-erythrocyte (BFU-E). No clonogenic breast cancer cells could be detected. Immunotoxin treatment eliminated 2.2 to 5.4 logs of clonogenic breast cancer cells, but had no effect on the bone marrow precursors. In seven of ten experiments, however, clonogenic breast cancer cells remained after immunotoxin treatment. Consequently, treatment with 4-HC, multiple murine monoclonal antibodies and magnetic microspheres provided more consistent elimination of tumor cells than separation with immunotoxins, but was significantly more toxic for marrow precursors.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: K C
authors.initials: KC
authors.lastname: O'Briant
authors.forename: E J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: L L
authors.initials: LL
authors.lastname: Houston
authors.forename: W P
authors.initials: WP
authors.lastname: Peters
authors.forename: R C
authors.initials: RC
authors.lastname: Bast
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D001856:Bone Marrow Examination / Q000379:methods; D016026:Bone Marrow Transplantation; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002469:Cell Separation / Q000379:methods*; D002999:Clone Cells; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008280:Magnetics; D008863:Microspheres; D014182:Transplantation, Autologous; D014410:Tumor Stem Cell Assay / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D003520:Cyclophosphamide; C011272:perfosfamide