Characteristics of the specific humoral response in patients with advanced solid tumors after active immunotherapy with a VEGF vaccine, at different antigen doses and using two distinct adjuvants

Autor: Javier Sánchez Ramírez, Yanelys Morera Díaz, Mónica Bequet-Romero, Francisco Hernández-Bernal, Katty-Hind Selman-Housein Bernal, Ana de la Torre Santos, Eduardo Rafael Santiesteban Álvarez, Yenima Martín Bauta, Cimara H. Bermúdez Badell, Josué de la Torre Pupo, Jorge V. Gavilondo, CENTAURO-2 Team of Investigators, Marta Ayala Avila
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: BMC Immunology, Vol 18, Iss 1, Pp 1-20 (2017)
Druh dokumentu: article
ISSN: 1471-2172
DOI: 10.1186/s12865-017-0222-z
Popis: Abstract Background CIGB-247, a VSSP-adjuvanted VEGF-based vaccine, was evaluated in a phase I clinical trial in patients with advanced solid tumors (CENTAURO). Vaccination with the maximum dose of antigen showed an excellent safety profile, exhibited the highest immunogenicity and was the only one showing a reduction on platelet VEGF bioavailability. However, this antigen dose level did not achieve a complete seroconversion rate in vaccinated patients. These clinical results led us to the question whether a “reserve” of untapped immune response potential against VEGF could exist in cancer patients. To address this matter, CENTAURO-2 clinical trial was conducted where antigen and VSSP dose scale up were studied, and also incorporated the exploration of aluminum phosphate as adjuvant. These changes were made with the aim to increase immune response against VEGF. Results The present study reports the characterization of the humoral response elicited by CIGB-247 from the combining of different antigen doses and adjuvants. Cancer patients were immunologically monitored for approximately 1 year. Vaccination with different CIGB-247 formulations exhibited a very positive safety profile. Cancer patients developed IgM, IgG or IgA antibodies specific to VEGF. Elicited polyclonal antibodies had the ability to block the interaction between VEGF and its receptors, VEGFR1 and VEGFR2. The highest humoral response was detected in patients immunized with 800 μg of antigen + 200 μg of VSSP. Off-protocol long-term vaccination did not produce negative changes in humoral response. Conclusions Vaccination with a human VEGF variant molecule as antigen in combination with VSSP or aluminum phosphate is immunogenic. The results of this study could contribute to the investigation of this vaccine therapy in an adequately powered efficacy trial. Trial registration Trial registration number: RPCEC00000155. Cuban Public Clinical Trial Registry. Date of registration: June 06, 2013. Available from: http://registroclinico.sld.cu/ .
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