Does VEGF-targeted active immunotherapy induce complete abrogation of platelet VEGF levels?

Abstract

Objectives Vascular endothelial growth factor (VEGF) is involved in physiological angiogenesis, but also is considered one of the key factors that promotes tumor angiogenesis. CIGB-247 is a VEGF-based vaccine that has been evaluated in phase I clinical trial patients with advanced solid tumors. This specific active immunotherapy is able to reduce platelet VEGF levels; however it is unknown whether this effect leads to a decrease in VEGF below the levels that can be observed in healthy individuals. The objective of the present study is to investigate platelet VEGF levels in cancer patients vaccinated with CIGB-247, and then compare these values with those obtained in healthy individuals. To achieve this, platelet VEGF levels of 62 cancer patients and 93 healthy individuals were compared. Cancer patients were those individuals recruited in CENTAURO and CENTAURO-2 clinical trials. Results Before vaccination, platelets of cancer patients carried more VEGF than the levels seen in platelet of healthy individuals. However, after vaccination, cancer patients had platelet VEGF values within the range established by healthy individuals, indicating that the antibody response elicited by CIGB-247 is not able to induce a complete suppression of VEGF. Vaccination with CIGB-247 helps to normalize VEGF levels within platelets. Electronic supplementary material The online version of this article (10.1186/s13104-019-4368-z) contains supplementary material, which is available to authorized users.

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program

“…It is know that bevacizumab treatment increases the risk of bleeding and wound healing complications in cancer patients [54]. These clinical observations with CIGB-247 could be explained by the incomplete abrogation of platelet VEGF levels after immunization with CIGB-247 [55]. After vaccination, remaining active VEGF molecules within platelets are probably sufficient to maintain the recovery response in wound healing, normal adult vasculature or other VEGF-dependent normal physiological processes.…”

“…Mandatory and programmed blood sample collections were not required in the CIGB-247 CUP, and these elements were optional and subjected to the physician's criteria, limiting the number of immunogenicity tests. Also, during the routine clinical evaluation of CUP patients, the blood sample collection, processing, handling and storage (− 20°C) of serum and plasma were suitable for antibody tests (immunoglobulin classes, IgG subclasses and blocking activity vs VEGFR2 and VEGFR1); however these conditions are not appropriate for VEGF quantification in serum and plasma, needing a storage temperature of − 70°C [55].…”

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.

“…Venous blood samples were collected using a blood collection set with pre-attached holder and taken into a serum separator tube for serum analyses. Serum samples were obtained as previously described [27,28], and were immediately stored at -20ºC or -70ºC until use.…”

“…It is know that bevacizumab treatment increases the risk of bleeding and wound healing complications in cancer patients [58]. These clinical observations with CIGB-247 could be explained by the incomplete abrogation of platelet VEGF levels after immunization with CIGB-247 [27]. After vaccination, remaining active VEGF molecules within platelets are probably sufficient to maintain the recovery response in wound healing, normal adult vasculature or other VEGF-dependent normal physiological processes.…”

“…immunogenicity tests. Also, during the routine clinical evaluation of CUP patients, the blood sample collection, processing, handling and storage (-20ºC) of serum and plasma were suitable for antibody tests (immunoglobulin classes, IgG subclasses and blocking activity vs VEGFR2 and VEGFR1); however these conditions are not appropriate for VEGF quantification in serum and plasma, needing a storage temperature of -70ºC[27].On the other hand, between 50 and 60 mL of blood is required for isolation of PBMC by Ficoll density gradient. This volume of blood is at least five times higher than the volume used for routine clinical monitoring of cancer patients.…”