Abstract
High dose chemotherapy with autologous bone marrow transplantation (ABMT) has shown promise in several types of cancer. There is, however, a risk of transfusing contaminating tumour cells with the bone marrow cells, e.g. in patients with small cell lung carcinoma (SCLC). To eliminate SCLC cells from normal human bone marrow, four monoclonal antibodies reactive with SCLC cells were used with immunomagnetic beads in model experiments. With two cycles of immunomagnetic elimination the individual antibodies removed 2.5-4.4 log of H-146 tumour cells from a single cell suspension, as assessed in a highly reproducible soft agar assay. Different combinations of two antibodies were only marginally more effective than the individual MAbs, whereas 5-6 log removal was obtained with a combination of all four antibodies. The method was equally effective when the tumour cells were mixed with bone marrow cells at a ratio of 1:10. The immunomagnetic procedure did not significantly affect the survival of normal progenitor cells, assessed in CFU-GM and CFU-GEMM assays. The results indicate that the procedure safely and effectively can be used to eliminate tumour cells from the bone marrow in conjunction with ABMT in patients with SCLC.
Highlights
Human bone marrow aspirates were obtained from healthy volunteers or from patients at the Norwegian Radium Hospital with non-small cell lung carcinoma (SCLC) malignancies that were free of tumour cells in their marrow
When different numbers of H-146 cells were seeded out in soft agar the number of colonies formed was proportional to the number of cells plated (Figure 1)
Similar curves were established in each model experiment, and the curves were used to calculate the tumour cell depletion obtained by the treatment, taking the plating efficiency in each experiment into account
Summary
Human bone marrow aspirates were obtained from healthy volunteers or from patients at the Norwegian Radium Hospital with non-SCLC malignancies that were free of tumour cells in their marrow. All samples were obtained with informed consent from the donors. Ten ml of bone marrow were layered upon Lymphoprep (Nycomed, Oslo, Norway) and the mononuclear cell fraction was obtained by centrifugation at 1200 r.p.m. for 30 min. The mononuclear cells were washed once in phosphate buffered saline (PBS) before being used in the experiments. The H-146 human SCLC cell line (Carney et al, 1985), kindly provided by Dr Adi F. National Cancer Institute, Bethesda, MD, USA, was used in the experiments. The cells were grown as suspension cultures in RPMI 1640 medium (Gibco, Paisley, UK) supplemented with 10% foetal calf serum (FCS)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
