Abstract
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.
Highlights
Pathological angiogenesis is one of the hallmarks of cancer [1]
Vascular endothelial growth factor (VEGF) baseline levels and hematological status of the patients recruited for CENTAURO and CENTAURO-2 clinical trials
Serum and plasma VEGF levels as well as hematocrit values and platelet counts are parameters included in the different VEGF measurement approaches (Table S1)
Summary
Pathological angiogenesis is one of the hallmarks of cancer [1]. Tumor-associated neovasculature, generated by the sprouting of new vessels from existing ones, is the source of nutrients and oxygen, indispensables for tumor expansion. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenesis inducers, and is usually elevated in various types of tumor as well as in the circulation of cancer patients [2]. Achieving predictability of therapeutic efficacy by measuring the decrease of the VEGF molecule is one the hardest goals to reach in passive or active immunotherapies directed to VEGF. Some authors have preferably used serum samples [7] and others plasma instead of serum [8] because plasma VEGF levels have been considered a better assessment of any circulating VEGF released by the tumor [9, 10]
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