Purging of epithelial tumor cells from peripheral blood stem cells by means of the bispecific antibody BIS-1
| Autor: | C P, Schröder, B J, Kroesen, L F, de Leij, E G, de Vries |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Lung Neoplasms
CD3 Complex Stem Cells T-Lymphocytes Antibodies Monoclonal Granulocyte-Macrophage Colony-Stimulating Factor Breast Neoplasms CD8-Positive T-Lymphocytes Flow Cytometry Lymphocyte Activation Immunohistochemistry Antibodies Chromium Radioisotopes Tumor Cells Cultured Humans Interleukin-2 Female Immunotherapy Neoplasms Glandular and Epithelial Glycoproteins |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 6(6) |
| ISSN: | 1078-0432 |
| Popis: | Peripheral blood stem cell (PBSC) support in breast cancer patients allows high-dose chemotherapy, but tumor cell contamination of the PBSCs is a potential source of relapse. Specific carcinoma cell killing can be obtained by retargeting activated T cells with bispecific antibody BIS-1, directed against epithelial glycoprotein-2 and CD3. To purge epithelial tumor cells from the PBSCs of breast cancer patients, activation of T cells in PBSCs and T-cell retargeting by BIS-1 was studied. PBSCs, obtained by leukapheresis after chemotherapy and recombinant human granulocyte colony-stimulating factor, were cultured in the presence of PBS, interleukin-2, OKT3, or interleukin-2/OKT3 for induction of T-cell activation. Subsequently, lysis of epithelial tumor cell lines by activated T cells of PBSCs in the presence or absence of BIS-1 was assessed with the 51Cr-release assay or immunocytochemical staining. The effect on PBSC hematopoietic colony formation (HCF) was evaluated by the granulocyte macrophage colony-stimulating units assay. Prior to activation, PBSCs from breast cancer patients contained higher levels of CD8+ T cells than peripheral blood from healthy volunteers (P0.05). The potential of PBSCs to sustain tumor cell lysis was increased after all prior activations and was further enhanced by BIS-1. Maximal BIS-1 effect was observed after OKT3 activation of PBSCs for 72 h (P0.0005), inducing a3 log depletion of tumor cells. HCF was not affected by prior OKT3 activation and/or BIS-1. In conclusion, specific tumor cell lysis by PBSCs can be obtained in vitro by OKT3 activation and BIS-1 retargeting of T cells, without affecting HCF. At present, studies are evaluating this format for future clinical application. |
| Databáze: | OpenAIRE |
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