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- Ullenhag, G, et al.
(författare)
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Incidence of GM-CSF antibodies in cancer patients receiving GM-CSF for immunostimulation.
- 2001
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 99, s. 65-
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Sun, Jia-Bin, 1948, et al.
(författare)
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Vaccination with dendritic cells pulsed in vitro with tumor antigen conjugated to cholera toxin efficiently induces specific tumoricidal CD8+ cytotoxic lymphocytes dependent on cyclic AMP activation of dendritic cells.
- 2004
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Ingår i: Clinical immunology (Orlando, Fla.). - : Elsevier BV. - 1521-6616. ; 112:1, s. 35-44
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the development of CD8+ tumor-specific cytotoxic lymphocytes (CTL) and protection against tumor growth after vaccination with bone marrow-derived dendritic cells (DC) pulsed with a model protein ovalbumin conjugated to cholera toxin (OVA-CT) in B6 mice using E.G7 tumor cells expressing OVA(257-264) peptide (SIINFEKL) as target cells in vitro and in vivo. Vaccination with OVA-CT-pulsed DC concurrently induced strong CTL in vitro activity and anti-E.G7 tumor protection in vivo in WT, NK-depleted and CD4-deficient mice as well as in IL-12-/- and IFN-gamma-/- mice but not in CD8-deficient mice. Importantly, activation of CTL by OVA-CT-pulsed DC was dependent on CT-induced activation of adenylate cyclase and increased cAMP production by DC associated with increased expression of MHC class I and co-stimulatory molecules (CD80, CD86 and CD40). These results show that vaccination with DC pulsed with antigens (Ag) conjugated to CT induces a strong CTL response and suggest that conjugation of tumor Ag to CT for DC vaccination represents a promising approach for tumor vaccination and immunotherapy.
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