Incidence of GM-CSF antibodies in cancer patients receiving GM-CSF for immunostimulation.
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.
Ullenhag
G
G
CancerCentreKarolinska, Karolinska Hospital, Stockholm, Sweden.
Bird
C
C
Ragnhammar
P
P
Frödin
J E
JE
Strigård
K
K
OIsterborg
A
A
Thorpe
R
R
Mellstedt
H
H
Wadhwa
M
M
D000906:Antibodies / Q000097:blood*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007114:Immunization; D015151:Immunoblotting; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000906:Antibodies; D014614:Vaccines, Synthetic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor