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At least 127 records · Page 7Linked to original sources
PubMed1990

Lectin-binding properties of Burkitt's lymphoma cell lines: application to bone marrow purging.

The efficacy of binding of several lectins to different Burkitt's lymphoma (BL) cell lines was investigated. Soybean agglutinin (SBA), peanut agglutinin (PNA), wheat germ agglutinin (WGA), and Sambucus nigra agglutinin (SNA) bound strongly to all BL cell lines. Because SBA has been used safely in clinical bone marrow transplantation (BMT) as part of the procedure for T-cell depletion and hence does not bind to the stem cells, we chose this lectin to establish a model for purging BL cells from human bone marrow. Using a two-step purging procedure with tumor cell agglutination by SBA in solution, a 2-log depletion could be accomplished. Using SBA-coated magnetic beads, we could improve BL cell depletion to greater than 4 logs. Because SBA seems to have a broad specificity for BL cells with concomitant enrichment in hematopoietic progenitor cells, the use of SBA-coated magnetic beads could be of interest for autologous BMT for lymphomas as well as other hematological malignancies and solid tumors with positive binding to SBA.

Agglutination↗
PubMed1986

Bone marrow purging procedure in Burkitt lymphoma with monoclonal antibodies and complement: quantification by a liquid cell culture monitoring system.

Using B1, Y29/55 and AL2 monoclonal antibodies (MoAbs) to target Burkitt lymphoma (BL) cell lines, we defined optimal conditions to lyse, in the presence of baby rabbit complement, BL cells in excess bone marrow (BM). After the purging procedure, down to one residual BL cell in 10(6) normal ones was detectable with a liquid cell culture assay. Using a cocktail of three MoAbs, on five different cell lines were observed more than 4 log BL cell depletion in samples contaminated with 1% BL cells and only one failure of the procedure on 17 experiments. However, a sixth line was constantly resistant to the procedure.

Animals↗
PubMed1997

Expression of exogenous wt-p53 does not affect normal hematopoiesis: implications for bone marrow purging.

Some gene therapy approaches for cancer treatment attempt to transduce onco-suppressor genes into tumor cells. A central problem of this strategy is the targeting of tumor cells to avoid damage to normal ones. It has been noticed that transduction of wt-p53 into a large number of cancer cells induces tumor suppression. In contrast, some observations suggest that introduction of exogenous wt-p53 into nontransformed cells does not impair proliferation. If normal bone marrow (BM) cells are not affected by wt-p53 transduction, BM purging from p53-responding leukemic cells might be achieved in vitro by delivering the wild-type onco-suppressor to all marrow cells. We undertook a series of experiments to assess whether transduction of wt-p53 into normal hematopoietic cells is harmful. Two different wt-p53-recombinant retroviruses were used to infect primary, murine BM cells. Expression of exogenous wt-p53 in these cells did not affect in vitro colony formation, and did not induce any observable effects on morphology and differentiation. In contrast, the same viruses suppressed the tumor phenotype of v-src-transformed 32D cells. These results might open the way to gene therapy approaches to leukemias with the p53 gene without the need to target specifically and uniquely the tumor cells, sparing the normal ones.

Bone Marrow Cells↗
PubMed1988

Induction of immune resistance against L1210 lymphatic leukemia in mice after chemoradiotherapy of the leukemia and reconstitution with bone marrow purged from the leukemia with mafosfamide.

Lymphatic leukemia L1210-bearing semisyngeneic Balb/c x DBA/2Wf F1 (CD2F1) mice were subjected to chemoradiotherapy (2 x 100 mg/kg of cyclophosphamide i.p. and 1000 cGy of total body irradiation) and reconstitution with 10(7) syngeneic bone marrow cells i.v. The bone marrow obtained from leukemic mice was previously ex vivo purged of the leukemia cells with mafosfamide (ASTA Z7654) and stored in liquid nitrogen. Eight weeks after cytoreductive therapy and bone marrow transplantation we tried to immunize the mice against the lethal dose of the leukemia by i.p. injections of L1210-Maf cells (L1210 cells treated in vitro with mafosfamide for inhibition of their growth). About 75% of such mice were able to reject the subsequent 10(3) L1210 leukemia cell challenge, as compared with 70% of normal immunized mice and 55% of mice reconstituted with bone marrow cells not treated with mafosfamide.

Animals↗
PubMed1990

Pre-clinical evaluation of anti-lacto-N-fucopentaose III (CD15) monoclonal antibodies for ex vivo bone marrow purging in acute myeloid leukemia.

In order to eliminate residual leukemic cells from the marrow of patients with acute myeloid leukemia (AML) prior to autologous bone marrow transplantation, the optimal conditions of utilization of three CD15 murine monoclonal antibodies (MoAb) were investigated. The VIM-D5 MoAb was used with rabbit complement (C'), whereas the 8.27 and SMY15A MoAbs were used in the presence of human C'. These antibodies were also tested after fixation on magnetic beads. In a culture assay in semi-solid medium with a mixture of normal marrow and 1% HL60 cells, a lysis of clonogenic cells greater than 99% was achieved with the three antibodies and two rounds of complement, or with antibody-coated magnetic beads. Cultures of leukemic clonogenic cells (CFU-L) were performed in 47 cases. An inhibition equal to or greater than 90% was achieved in seven cases with VIM-D5, 16 cases with 8.27 and 11 cases with SMY15A and C'. The correlation with cytotoxicity of fresh cells was low. Twenty cases were purged with antibody-coated beads. An inhibition equal to or greater than 90% was observed in 10 cases with VIM-D5, 11 cases with 8.27 and 12 cases with SMY15A. The mean recovery of normal CFU-GM was higher than 70% and that of BFU-E higher than 95% with any method of treatment. It is concluded that efficient marrow purging of clonogenic AML cells can be achieved in some cases without toxicity for normal progenitors. The addition of other MoAbs seems necessary to obtain a significant purge in a majority of cases.

Antibodies, Monoclonal↗
PubMed1989

Bone marrow purging for multiple myeloma by avidin-biotin immunoadsorption.

Avidin-biotin immunoadsorption, a technique based on the high affinity between the protein avidin and the vitamin biotin, has been used to remove neoplastic plasma cells from the bone marrow of patients with multiple myeloma. Buffy coat cells obtained from 25 patients were first incubated with monoclonal antibodies (MoAb) capable of recognizing plasma cell-associated antigens (i.e., 8A, 8F6, 62B1, and cocktails of 8A plus 8F6 or 62B1), then with biotinylated goat antimouse immunoglobulin, and passed over a column containing avidin conjugated to Sepharose GMB. Both non-linked and linked cells were analyzed by immunofluorescence and morphological staining. The results showed that over 98% of plasma cells were removed by using 8A or 8F6 alone, while 99.5% +/- 0.4 SD of plasma cell purging was achieved with 2 associated MoAb. In addition, the overall recovery of committed granulocyte-macrophage (CFU-GM),* erythroid (BFU-e), and multilineage (CFU-GEMM) progenitors after column treatment ranged from 39% +/- 15 SD to 50% +/- 6 SD, from 15% +/- 2 SD to 39% +/- 7 SD, and from 16 +/- 4 SD to 64% +/- 10 SD, according to the MoAb employed. On this basis avidin-biotin immunoadsorption appears to be a suitable technique for ex-vivo manipulation of bone marrow infiltrated by neoplastic plasma cells.

Antibodies, Monoclonal↗
PubMed1990

In vitro bone marrow purging of multidrug-resistant cells with a mouse monoclonal antibody directed against Mr 170,000 glycoprotein and a saporin-conjugated anti-mouse antibody.

Selective elimination of multidrug resistance-positive cells (LoVo/Dx) was obtained by using the monoclonal antibody MRK 16, which recognizes a surface epitope of the Mr 170,000 glycoprotein, and a sheep anti-mouse immunoglobulin antibody, conjugated to the ribosome-inactivating protein saporin 6. The killing was greatly decreased or even abolished by adding the monoclonal antibody at a 100-fold concentration. Both the MRK 16 and anti-mouse saporin 6 conjugate did not show any killing activity when they were used separately. In cell suspensions composed of 90% normal bone marrow cells and 10% multidrug resistance-positive cells, the monoclonal antibody MRK 16 followed by the anti-mouse immunotoxin caused the elimination of 99% multidrug resistance-positive cells, as revealed by immunofluorescence and immunocytochemistry as well as by a clonal assay. Human normal hematopoietic precursors (granulomonocytic colony-forming units, erythroid burst-forming units, and multipotent granulomonocytic, erythroid, and megakaryocytic-forming units) were not affected by the MRK 16 plus immunotoxin treatment. This technique might be suitable for ex vivo bone purging in an appropriate clinical setting, such as autologous bone marrow transplantation.

Antibodies, Monoclonal↗