Incidence of GM-CSF Antibodies in Cancer Patients Receiving GM-CSF for Immunostimulation
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文摘
We have assessed the immunogenicity profile of GM-CSF in patients with either colorectal carcinoma (CRC) at different stages of disease or with multiple myeloma who were given recombinant human GM-CSF (Escherichia coli-derived) combination therapy. Metastatic CRC patients received a colon carcinoma-reactive antibody and high doses of GM-CSF (425–500 μg/day for 10 days), while other CRC patients and those with myeloma received low doses of GM-CSF (75–80 μg/day for 4 days) as an adjuvant along with appropriate tumor antigens. We found that 55 % of the patients (11/20) given high doses of GM-CSF developed GM-CSF-reactive antibodies in comparison with an incidence of only 16 % (4/25) in patients given low doses of GM-CSF. None of the patients developed neutralizing antibodies and so the biological effects of GM-CSF were not compromised. A majority of patients (80 % ) (36/45) also developed antibodies to E. coli proteins that were present as trace contaminants in the GM-CSF product. Treatment with recombinant GM-CSF products, therefore, may induce antibodies against this cytokine depending on the regimen and the amounts used. In this study, multiple immunizations with low doses of GM-CSF was associated with a low incidence of GM-CSF antibodies, which did not neutralize the effect of the cytokine. This therapeutic strategy was effective in inducing adjuvant-type effects and needs to be explored in further clinical trials with this cytokine.

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