Journal article
Recombinant bacille Calmette–Guérin (BCG) expressing human interferon-alpha 2B demonstrates enhanced immunogenicity
Clinical and experimental immunology, Vol.123(2), pp.264-270
12/20/2001
DOI: 10.1046/j.1365-2249.2001.01428.x
PMCID: PMC1905993
PMID: 11207657
Abstract
SUMMARY
To increase its immunostimulatory properties, BCG was genetically engineered to secrete recombinant human interferon-alpha 2B (rhIFN-α) under control of the mycobacterial heat shock protein (hsp)60 promoter and the α antigen signal sequence. Expression of rhIFN-α was readily detectable by ELISA and on Western blotting. When compared with control BCG, rhIFN-α BCG was substantially more active in inducing the production of IFN-γ and IFN-inducible protein 10 (IP-10) from human peripheral blood mononuclear cells, while IL-10 production was correspondingly decreased. These effects were reversible upon antibody neutralization of rhIFN-α. Among 10 patients tested, rhIFN-α BCG enhanced IFN-γ production in all patients ranging from 1·4- to 23·7-fold with a general trend toward greatest enhancement among those with weakest baseline responses to control BCG. Correspondingly, rhIFN-α BCG decreased IL-10 production in all patients by 1·2–4·8-fold. The onset of IFN-γ production induced by rhIFN-α BCG was also more rapid, occurring within 4 h after stimulation versus > 24 h with wild-type BCG. The observation that the maximum IFN-γ induction depends on the simultaneous presence of both IFN-α and BCG highlights the advantages of rhIFN-α BCG. Taken together, these immunostimulatory properties of rhIFN-α BCG suggest that it may be a superior agent for immunotherapeutic protocols involving live BCG in humans.
Details
- Title: Subtitle
- Recombinant bacille Calmette–Guérin (BCG) expressing human interferon-alpha 2B demonstrates enhanced immunogenicity
- Creators
- Y Luo - Beth Israel Deaconess Medical CenterX Chen - Beth Israel Deaconess Medical CenterR Han - Beth Israel Deaconess Medical CenterM A O'Donnell - Beth Israel Deaconess Medical Center
- Resource Type
- Journal article
- Publication Details
- Clinical and experimental immunology, Vol.123(2), pp.264-270
- DOI
- 10.1046/j.1365-2249.2001.01428.x
- PMID
- 11207657
- PMCID
- PMC1905993
- ISSN
- 0009-9104
- eISSN
- 1365-2249
- Language
- English
- Date published
- 12/20/2001
- Academic Unit
- Urology
- Record Identifier
- 9984320070902771
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