Evaluation of methodologies to determine the effect of specific active immunotherapy on VEGF levels in phase I clinical trial patients with advanced solid tumors
Two phase I clinical trials were conducted to evaluate, among other parameters, the humoral response elicited by a vascular endothelial growth factor (VEGF)-based therapeutic vaccine in cancer patients with advanced solid tumors. VEGF reduction was studied using an indirect methodology named as “Pla...
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Elsevier
2018-11-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844018317699 |
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author | Javier Sánchez Ramírez Mónica Bequet-Romero Yanelys Morera Díaz Francisco Hernández-Bernal Ana de la Torre Santos Katty-Hind Selman-Housein Bernal Yenima Martín Bauta Cimara H. Bermúdez Badell Miladys Limonta Fernández Marta Ayala Avila |
author_facet | Javier Sánchez Ramírez Mónica Bequet-Romero Yanelys Morera Díaz Francisco Hernández-Bernal Ana de la Torre Santos Katty-Hind Selman-Housein Bernal Yenima Martín Bauta Cimara H. Bermúdez Badell Miladys Limonta Fernández Marta Ayala Avila |
author_sort | Javier Sánchez Ramírez |
collection | DOAJ |
description | Two phase I clinical trials were conducted to evaluate, among other parameters, the humoral response elicited by a vascular endothelial growth factor (VEGF)-based therapeutic vaccine in cancer patients with advanced solid tumors. VEGF reduction was studied using an indirect methodology named as “Platelet VEGF”. This methodology is based on the estimation of VEGF within platelets by subtracting the plasma VEGF level from the serum level and dividing this by the platelet count, and then this latter expression is additionally corrected by the hematocrit. However, there is broad debate, whether serum or plasma VEGF or platelet-derived VEGF measurements is the most appropriate strategy to study the changes that occur on ligand bioavailability when patients are submitted to a VEGF-based immunotherapy.The current research is a retrospective study evaluating the changes on VEGF levels in serum and plasma as well as platelet-derived measurements. Changes in VEGF levels were related with the humoral response seen in cancer patients after an active immunotherapy with a VEGF-based vaccine. The present study indicates that “Platelet VEGF” is the most reliable methodology to investigate the effect of VEGF-based immunotherapies on ligand bioavailability. “Platelet VEGF” was associated with those groups of individuals that exhibited the best specific humoral response and the variation of “Platelet VEGF” showed the strongest negative correlation with VEGF-specific IgG antibody levels. This methodology will be very useful for the investigation of this VEGF-based vaccine in phase II clinical trials and could be applied to immunotherapies directed to other growth factors that are actively sequestered by platelets. |
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spelling | doaj.art-d0323fe1dd8d4e3986f5db7d9bee6cb42022-12-21T20:32:30ZengElsevierHeliyon2405-84402018-11-01411e00906Evaluation of methodologies to determine the effect of specific active immunotherapy on VEGF levels in phase I clinical trial patients with advanced solid tumorsJavier Sánchez Ramírez0Mónica Bequet-Romero1Yanelys Morera Díaz2Francisco Hernández-Bernal3Ana de la Torre Santos4Katty-Hind Selman-Housein Bernal5Yenima Martín Bauta6Cimara H. Bermúdez Badell7Miladys Limonta Fernández8Marta Ayala Avila9Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Playa, Havana, Cuba; Corresponding author.Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Playa, Havana, CubaDepartment of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Playa, Havana, CubaDepartment of Clinical Research, Center for Genetic Engineering and Biotechnology, Playa, Havana, Cuba“Celestino Hernández Robau” Hospital, Santa Clara, Villa Clara, CubaCenter of Medical and Surgical Research, Playa, Havana, CubaDepartment of Clinical Research, Center for Genetic Engineering and Biotechnology, Playa, Havana, CubaDepartment of Clinical Research, Center for Genetic Engineering and Biotechnology, Playa, Havana, CubaDepartment of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Playa, Havana, CubaDepartment of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Playa, Havana, CubaTwo phase I clinical trials were conducted to evaluate, among other parameters, the humoral response elicited by a vascular endothelial growth factor (VEGF)-based therapeutic vaccine in cancer patients with advanced solid tumors. VEGF reduction was studied using an indirect methodology named as “Platelet VEGF”. This methodology is based on the estimation of VEGF within platelets by subtracting the plasma VEGF level from the serum level and dividing this by the platelet count, and then this latter expression is additionally corrected by the hematocrit. However, there is broad debate, whether serum or plasma VEGF or platelet-derived VEGF measurements is the most appropriate strategy to study the changes that occur on ligand bioavailability when patients are submitted to a VEGF-based immunotherapy.The current research is a retrospective study evaluating the changes on VEGF levels in serum and plasma as well as platelet-derived measurements. Changes in VEGF levels were related with the humoral response seen in cancer patients after an active immunotherapy with a VEGF-based vaccine. The present study indicates that “Platelet VEGF” is the most reliable methodology to investigate the effect of VEGF-based immunotherapies on ligand bioavailability. “Platelet VEGF” was associated with those groups of individuals that exhibited the best specific humoral response and the variation of “Platelet VEGF” showed the strongest negative correlation with VEGF-specific IgG antibody levels. This methodology will be very useful for the investigation of this VEGF-based vaccine in phase II clinical trials and could be applied to immunotherapies directed to other growth factors that are actively sequestered by platelets.http://www.sciencedirect.com/science/article/pii/S2405844018317699Cancer researchImmunology |
spellingShingle | Javier Sánchez Ramírez Mónica Bequet-Romero Yanelys Morera Díaz Francisco Hernández-Bernal Ana de la Torre Santos Katty-Hind Selman-Housein Bernal Yenima Martín Bauta Cimara H. Bermúdez Badell Miladys Limonta Fernández Marta Ayala Avila Evaluation of methodologies to determine the effect of specific active immunotherapy on VEGF levels in phase I clinical trial patients with advanced solid tumors Heliyon Cancer research Immunology |
title | Evaluation of methodologies to determine the effect of specific active immunotherapy on VEGF levels in phase I clinical trial patients with advanced solid tumors |
title_full | Evaluation of methodologies to determine the effect of specific active immunotherapy on VEGF levels in phase I clinical trial patients with advanced solid tumors |
title_fullStr | Evaluation of methodologies to determine the effect of specific active immunotherapy on VEGF levels in phase I clinical trial patients with advanced solid tumors |
title_full_unstemmed | Evaluation of methodologies to determine the effect of specific active immunotherapy on VEGF levels in phase I clinical trial patients with advanced solid tumors |
title_short | Evaluation of methodologies to determine the effect of specific active immunotherapy on VEGF levels in phase I clinical trial patients with advanced solid tumors |
title_sort | evaluation of methodologies to determine the effect of specific active immunotherapy on vegf levels in phase i clinical trial patients with advanced solid tumors |
topic | Cancer research Immunology |
url | http://www.sciencedirect.com/science/article/pii/S2405844018317699 |
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