RESUMEN
The rational combination of recombinant IFN-α2b and IFN-γ resulted in a new formulation of interferons (HeberFERON) with improved pharmacodynamics. In basal cell carcinomas HeberFERON produces a more rapid antitumor effect and results in a larger number of complete responses. In patients with glioblastoma multiforme, the administration of HeberFERON after surgery and radiotherapy results in an estimated overall survival of 19 months. Patients with stage III or IV renal cell carcinoma also appear to benefit from the intravenous administration of HeberFERON, with prolongation of survival and good quality of live. HeberFERON offers a promising alternative formulation of interferons for the treatment of cancer with a very favorable safety profile.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interferón-alfa/uso terapéutico , Interferón gamma/uso terapéutico , Neoplasias/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/farmacocinética , Interferón gamma/administración & dosificación , Interferón gamma/farmacocinética , Neoplasias/genética , Neoplasias/metabolismo , Proteoma/metabolismo , Calidad de Vida , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Recombinant simian IL-15 (siIL-15) was obtained for the preclinical assessment of an anti-human IL-15 vaccine. For this purpose, the cDNA from peripheral blood mononuclear cells of a Macaca fascicularis monkey was cloned into a pIL-2 vector. The siIL-15 was expressed in Escherichia coli strain W3110 as an insoluble protein which accounted for 13% of the total cellular proteins. Inclusion bodies were solubilized in an 8 M urea solution, which was purified by ion exchange and reverse phase chromatography up to 92% purity. The protein identity was validated by electrospray ionization-mass spectrometry, confirming the presence of the amino acids which distinguish the siIL-15 from human IL-15. The purified siIL-15 stimulates the proliferation of cytotoxic T-lymphocytes line (CTLL)-2 and Kit 225 cells with EC50 values of 3.1 and 32.5 ng/mL, respectively. Antisera from modified human IL-15-immunized macaques were reactive to human and simian IL-15 in enzyme-linked immunosorbent assays. Moreover, the anti-human IL-15 antibodies from immune sera inhibited siIL-15 activity in CTLL-2 and Kit 225 cells, supporting the activity and purity of recombinant siIL-15. These results indicate that the recombinant siIL-15 is biologically active in two IL-15-dependent cell lines, and it is also suitable for the preclinical evaluation of an IL-15-based therapeutic vaccine.