Recombinant bacille Calmette-Guérin (BCG) expressing human interferon-alpha 2B demonstrates enhanced immunogenicity.
To increase its immunostimulatory properties, BCG was genetically engineered to secrete recombinant human interferon-alpha 2B (rhIFN-alpha) under control of the mycobacterial heat shock protein (hsp)60 promoter and the alpha antigen signal sequence. Expression of rhIFN-alpha was readily detectable by ELISA and on Western blotting. When compared with control BCG, rhIFN-alpha BCG was substantially more active in inducing the production of IFN-gamma 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-alpha. Among 10 patients tested, rhIFN-alpha BCG enhanced IFN-gamma 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-alpha BCG decreased IL-10 production in all patients by 1.2-4.8-fold. The onset of IFN-gamma production induced by rhIFN-alpha BCG was also more rapid, occurring within 4 h after stimulation versus > 24 h with wild-type BCG. The observation that the maximum IFN-gamma induction depends on the simultaneous presence of both IFN-alpha and BCG highlights the advantages of rhIFN-alpha BCG. Taken together, these immunostimulatory properties of rhIFN-alpha BCG suggest that it may be a superior agent for immunotherapeutic protocols involving live BCG in humans.
Luo
Y
Y
Division of Urology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Chen
X
X
Han
R
R
O'Donnell
M A
MA
D001500:BCG Vaccine; D015870:Gene Expression; D006801:Humans; D007167:Immunotherapy; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000235:genetics* / Q000276:immunology; D009163:Mycobacterium bovis / Q000235:genetics* / Q000276:immunology*; D011994:Recombinant Proteins; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy
D001500:BCG Vaccine; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins