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

Abstract

Background: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine. Results: Polyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 μg of antigen combined with 200 μg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP. The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-today clinical practice and treatment settings for these diseases in Cuban medical institutions.

TME-Related Biomimetic Strategies Against Cancer

“…39 During malignant tumor progression, angiogenesis remains in a normal state. 39,40 When the tumor grows, due to higher oxygen and nutrient demand, continuous new angiogenesis progresses to fulfill the metabolic demand of tumorous cells, thus, making angiogenesis a process of pivotal importance for tumor growth and metastasis. 41 Blood vessels in tumors are also structurally different from those in normal tissues.…”

Progress in Natural Compounds/siRNA Co-delivery Employing Nanovehicles for Cancer Therapy

“…Small interfering RNA may be used to knockout the genes involved in malignancy. Vascular endothelial growth factor (VEGF) is an oncogene involved in enhancing tumor neovascularization and is up-regulated in different types of cancer. , Because of the role of VEGF in promoting cancer growth and viability, studies have been performed on the inhibition of VEGF expression in anticancer therapy. , The combination of siRNA–VEGF and etoposide appears to be beneficial in the treatment of lung cancer. Multifunctional nanoparticles have been used as platforms for coloading of siRNA–VEGF and etoposide.…”

“…357,358 Because of the role of VEGF in promoting cancer growth and viability, studies have been performed on the inhibition of VEGF expression in anticancer therapy. 359,360 The combination of siRNA−VEGF and etoposide appears to be beneficial in the treatment of lung cancer. Multifunctional nanoparticles have been used as platforms for coloading of siRNA−VEGF and etoposide.…”