Potential mechanisms involved on how systemic IgG antibodies specific to vascular endothelial growth factor (VEGF) and induced by active immunotherapy decrease platelet derived free-VEGF

Abstract

CIGB-247 is a vascular endothelial growth factor (VEGF)-based active immunotherapy and it is currently under investigation for cancer treatment. This specific active immunotherapy encompasses two vaccine candidates that use a human VEGF variant molecule as antigen, in combination with two clinically tested adjuvants: VSSP or aluminum phosphate. CIGB-247 has been evaluated in patients with advanced solid tumors, recruited in two phase I clinical trials, and it has been shown to be safe and immunogenic by activating both cellular and humoral immune responses against human VEGF. The immunization induces specific IgG antibodies, and also shows as effect, the reduction of free-VEGF levels within platelets (platelet-derived free VEGF). The production of systemic IgG antibodies and the presence of VEGF in another compartment, almost exclusively within platelets, have arisen some questions about this effect detected in the vaccinated-cancer patients. Based on some relevant published works about platelet endocytosis and VEGF pharmacodynamics during bevacizumab treatment as well as the phase I clinical data of CIGB-247, this investigation aims to hypothesize and analyze the potential mechanisms involved in the reduction of platelet-derived free VEGF as a result of vaccination with CIGB-247.

Abbreviations: FcγR: Fc gamma receptors; IC: immune complexes; VEGF: vascular endothelial growth factor; VEGFR1: vascular endothelial growth factor receptor 1; VEGFR2: vascular endothelial growth factor receptor 2.

Keywords:

• Active immunotherapy
• CIGB-247
• endocytosis
• platelet
• VEGF
• α-granules

Authors’ contributions

JSR analyzed and interpreted the data and wrote the manuscript. YMD and MBR analyzed and interpreted the data and reviewed the manuscript. MAA was the project manager and took part in the interpretation of the results and reviewed the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

This investigation refers three studies of the evaluation of CIGB-247 in cancer patients. All of them were conducted in accordance with the ethical guidelines of the Declaration of Helsinki and approved by the Cuban Regulatory Authority. Written informed consent was obtained for all patients.

Disclosure statement

One author declares a financial competing interest. MBR is the inventor on a patent application submitted by the Center for Genetic Engineering and Biotechnology that covers the use of the vaccine.

Additional information

Funding

This work was supported by Heber Biotec and the Ministry of Public Health of Cuba. Both funders were involved in the design of the study and collection, analysis, and interpretation of data.