CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research

CK2 represents an oncology target scientifically validated. However, clinical research with inhibitors of the CK2-mediated phosphorylation event is still insufficient to recognize it as a clinically validated target. CIGB-300, an investigational peptide-based drug that targets the phosphoaceptor site, binds to a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB-300 proapoptotic effect is preceded by its nucleolar localization, inhibition of the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly. Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome biogenesis, cell proliferation, glycolisis, and cell motility in proteomic studies which helped to understand its mechanism of action. In the clinical ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human trial in women with cervical malignancies who also experienced signs of clinical benefit. In a second Phase 1 clinical trial in women with cervical cancer stage IB2/II, the MTD and DLT have been also identified in the clinical setting. Interestingly, in cervical tumors the B23/nucleophosmin protein levels were significantly reduced after CIGB-300 treatment at the nucleus compartment. In addition, expanded use of CIGB-300 in case studies has evidenced antitumor activity when administered as compassional option. Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology.Fil: Perea, Silvio E.. Center for Genetic Engineering and Biotechnology; CubaFil: Baladron, Idania. Center for Genetic Engineering and Biotechnology; CubaFil: Garcia, Yanelda. Center for Genetic Engineering and Biotechnology; CubaFil: Perera, Yasser. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Adlin. Center for Genetic Engineering and Biotechnology; CubaFil: Soriano, Jorge L.. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Batista, Noyde. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Palau, Aley. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Hernández, Ignacio. Center for Genetic Engineering and Biotechnology; CubaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Idrian. Center for Genetic Engineering and Biotechnology; CubaFil: Gonzalez, Lidia. Center for Genetic Engineering and Biotechnology; CubaFil: Gil, Jeovanis. Center for Genetic Engineering and Biotechnology; CubaFil: Rodriguez, Arielis. Center for Genetic Engineering and Biotechnology; CubaFil: Solares, Margarita. Center for Genetic Engineering and Biotechnology; CubaFil: Santana, Agueda. Center for Genetic Engineering and Biotechnology; CubaFil: Cruz, Marisol. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Matilde. Center for Genetic Engineering and Biotechnology; CubaFil: Valenzuela, Carmen. Center for Genetic Engineering and Biotechnology; CubaFil: Reyes, Osvaldo. Center for Genetic Engineering and Biotechnology; CubaFil: López Saura, Pedro A.. Center for Genetic Engineering and Biotechnology; CubaFil: González, Carlos A.. Center for Genetic Engineering and Biotechnology; CubaFil: Diaz, Alina. Center for Genetic Engineering and Biotechnology; CubaFil: Castellanos, Lila. Center for Genetic Engineering and Biotechnology; CubaFil: Sanchez, Aniel. Center for Genetic Engineering and Biotechnology; CubaFil: Betancourt, Lazaro. Center for Genetic Engineering and Biotechnology; CubaFil: Besada, Vladimir. Center for Genetic Engineering and Biotechnology; CubaFil: González, Luis J.. Center for Genetic Engineering and Biotechnology; CubaFil: Garay, Hilda. Center for Genetic Engineering and Biotechnology; CubaFil: Gómez, Roberto. Center for Genetic Engineering and Biotechnology; CubaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perrin, Phillipe. No especifíca;Fil: Renualt, Jean Yves. No especifíca;Fil: Sigman, Hugo. No especifíca;Fil: Herrera, Luis. Center for Genetic Engineering and Biotechnology; CubaFil: Acevedo, Boris. Center for Genetic Engineering and Biotechnology; Cub

Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

<p>Abstract</p> <p>Background</p> <p>Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC).</p> <p>Methods</p> <p>Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor.</p> <p>Results</p> <p>Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated.</p> <p>Conclusion</p> <p>The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials.</p> <p>Trial registration</p> <p>Current Controlled Trials RPCEC00000052.</p

HeberFERON, formulation based on IFNs alpha2b and gamma for the treatment of non-melanoma skin cancer

Background Surgery remains the procedure of election for the treatment of non-melanoma skin cancer (NMSC). However, after recurrence, or under surgical complex scenarios, other therapeutic modalities have to be indicated. Immune suppression is associated to NMSC; thus, immunotherapy is a rational approach to treat the high spread form of skin tumour. Aims We propose a summary of the most relevant clinical results with the combination of IFNs alpha2b and gamma in the treatment of non-melanoma skin cancer. Methods In several clinical trials (Open prospective trial; phase 2 double-blind randomized studies: InCarbacel-II and InCarbacel-III; retrospective study and ongoing phase IV trial, InCarbacel-IV) more than 200 patients with histological diagnostic of non-melanoma skin cancer were recruited to be treated with the combination of IFNs in Cuban health institutions at primary, secondary or tertiary care levels. All the studies were approved by institutional ethic committees and all the patients given their written informed consent. HeberFERON was administered, peri- or intralesionally, three times per week, during 3 weeks. Clinical and histological responses were evaluated by RECIST (1.0), three months after the end of treatment. Results HeberFERON promoted more rapid and higher number of CRs than separated IFNs (InCarbacel-II study). The openlabel prospective study showed 46.7 per cent CR in locally advanced BCC after application of HeberFERON. Patients with periocular BCC or SCSC received benefits from HeberFERON treatment (71.4 per cent OR). Overall, HeberFERON has been administered to patients with nonmelanoma skin cancer obtaining a 65 per cent of histological CR together with an excellent safety profile. Conclusion HeberFERON is a novel, non-surgical, effective and safe option to treat advanced, high risk or recurrent nonmelanoma skin cancer

HeberFERON, formulation based on IFNs alpha2b and gamma for the treatment of non-melanoma skin cancer

BackgroundSurgery remains the procedure of election for the treatment of non-melanoma skin cancer (NMSC). However, after recurrence, or under surgical complex scenarios, other therapeutic modalities have to be indicated. Immune suppression is associated to NMSC; thus, immunotherapy is a rational approach to treat the high spread form of skin tumour.AimsWe propose a summary of the most relevant clinical results with the combination of IFNs alpha2b and gamma in the treatment of non-melanoma skin cancer.Methods In several clinical trials (Open prospective trial; phase 2 double-blind randomized studies: InCarbacel-II and InCarbacel-III; retrospective study and ongoing phase IV trial, InCarbacel-IV) more than 200 patients with histological diagnostic of non-melanoma skin cancer were recruited to be treated with the combination of IFNs in Cuban health institutions at primary, secondary or tertiary care levels. All the studies were approved by institutional ethic committees and all the patients given their written informed consent. HeberFERON was administered, peri- or intralesionally, three times per week, during 3 weeks. Clinical and histological responses were evaluated by RECIST (1.0), three months after the end of treatment.Results HeberFERON promoted more rapid and higher number of CRs than separated IFNs (InCarbacel-II study). The open-label prospective study showed 46.7 per cent CR in locally advanced BCC after application of HeberFERON. Patients with periocular BCC or SCSC received benefits from HeberFERON treatment (71.4 per cent OR). Overall, HeberFERON has been administered to patients with non-melanoma skin cancer obtaining a 65 per cent of histological CR together with an excellent safety profile.ConclusionHeberFERON is a novel, non-surgical, effective and safe option to treat advanced, high risk or recurrent non-melanoma skin cancer