Incidence of GM-CSF antibodies in cancer patients receiving GM-CSF for immunostimulation.
2001 (English)In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 99, no 1, 65-74 p.Article in journal (Refereed) Published
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 microg/day for 10 days), while other CRC patients and those with myeloma received low doses of GM-CSF (75--80 microg/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.
Place, publisher, year, edition, pages
2001. Vol. 99, no 1, 65-74 p.
GM-CSF, antibodies, GM-CSF, immunostimulation, cancer
IdentifiersURN: urn:nbn:se:umu:diva-126908DOI: 10.1006/clim.2000.4999PubMedID: 11286542OAI: oai:DiVA.org:umu-126908DiVA: diva2:1038872