학술논문
Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.
Document Type
Article
Author
Sánchez Ramírez, Javier; Morera Díaz, Yanelys; Bequet-Romero, Mónica; Hernández-Bernal, Francisco; Martín Bauta, Yenima; Selman-Housein Bernal, Katty-Hind; de la Torre Santos, Ana Victoria; Pérez de la Iglesia, Mariela; Trimiño Lorenzo, Lian; Team of Investigators of Compassionate use Program; Gavilondo Cowley, Jorge Víctor; Limonta Fernández, Miladys; Padrón Morales, Sheila; Leal Alpízar, Giselle; Godínez Díaz, Duneidis; Rodríguez Reinoso, José Luis; Melo Suárez, Grettel; Muzio González, Verena Lucila; López Carrazana, Luis J.; Carreño Rolando, Ihosvany Enrique
Source
Subject
*IMMUNOTHERAPY
*CANCER patients
*VASCULAR endothelial growth factors
*IMMUNE serums
*VASCULAR endothelial growth factor receptors
*CANCER vaccines
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Language
ISSN
1471-2172
Abstract
Background: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine. Results: Polyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 μg of antigen combined with 200 μg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP. The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-to-day clinical practice and treatment settings for these diseases in Cuban medical institutions. Conclusions: The CIGB-247 CUP has demonstrated that immunization and follow-up of a variety of cancer patients, under day-to-day clinical practice conditions in several Cuban medical institutions, replicate our previous findings in clinical trials: CIGB-247 is safe and immunogenic. [ABSTRACT FROM AUTHOR]