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

Mónica Bequet-Romero¹  Yenima Martín Bauta²  Ana de la Torre Santos³  Cimara H. Bermúdez Badell³  Miladys Limonta Fernández³  Yanelys Morera Díaz⁴  Marta Ayala Avila⁴  Javier Sánchez Ramírez⁴  Francisco Hernández-Bernal⁴  Katty-Hind Selman-Housein Bernal⁵ 

[1] Corresponding author.;Center of Medical and Surgical Research, Playa, Havana, Cuba;Department of Clinical Research, Center for Genetic Engineering and Biotechnology, Playa, Havana, Cuba;Department of Pharmaceuticals, Center for Genetic Engineering and Biotechnology, Playa, Havana, Cuba;“Celestino Hernández Robau” Hospital, Santa Clara, Villa Clara, Cuba;

关键词: Cancer research;    Immunology;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown