A Pilot Study of the Adverse Events Caused by the Combined Use of Bevacizumab and Vascular Endothelial Growth Factor Receptor-Targeted Vaccination for Patients with a Malignant Glioma

Abstract

Anti-angiogenic therapy, targeting vascular endothelial growth factor (VEGF)-A/VEGF receptors (VEGFRs), is beneficial for tumor growth prevention in a malignant glioma. A simultaneous blockade using both bevacizumab (Bev), which targets circulating VEGF-A, and a multi-kinase inhibitor on VEGFRs was more effective for advanced solid cancers, including melanoma and renal cell carcinoma. However, previous clinical trials demonstrated a high adverse event rate. Additionally, no studies previously assessed treatment efficacy and safety using both VEGF-A and VEGFR-targeted agents for malignant gliomas. We had conducted clinical trials investigating VEGFRs peptide vaccination in patients with malignant gliomas, in which the treatment exhibited safety and yielded therapeutic effects in some patients. The combined use of Bev and VEGFRs vaccination may enhance the anti-tumor effect in malignant gliomas. In this pilot study, the adverse event profile in patients treated with Bev after the vaccination was investigated to establish this treatment strategy, in comparison to those treated with Bev collected from the published data or treated with the vaccination alone. In our previous clinical studies on patients with malignant gliomas, Bev was administered to 13 patients after VEGFRs vaccinations. One patient had a Grade 4 pulmonary embolism. Two patients had Grade 2 cerebral infarctions. There were no significant differences in the adverse event rates among patients treated with Bev, with the vaccination, or with Bev after the vaccination. Although careful observation is imperative for patients after this combination treatment strategy, VEGFRs-targeted vaccination may coexist with Bev for malignant gliomas.

Liposome Nanomedicine Based on Tumor Cell Lysate Mitigates the Progression of Lynch Syndrome-Associated Colon Cancer

“…In addition, some studies have attempted to combine tumor vaccines with ICIs to maximize the benefits of immunotherapy. , For example, Wang et al loaded tumor antigens and anti-PD-L1 antibodies onto hollow mesoporous silica (HMS) to treat mice, demonstrating significant anticancer effects and a significant reduction in the required dosage compared to using ICIs alone. Similar to the results obtained in this study, we injected MC38 Mlh1 KD into mice to establish a syngeneic tumor model and found that treatment with TCL combined with anti-PD-L1 antibodies prolonged overall survival and prevented cancer progression compared to single immunotherapy.…”

Phase I/II Study of a Vascular Endothelial Growth Factor Receptor Vaccine in Patients With NF2-Related Schwannomatosis

“…[32][33][34] In the retrospective study, adverse event rates did not significantly differ between patients treated with Bev, those treated with vaccination, and those treated with Bev after vaccination. 35 This combined strategy may be an option in patients with NF2.…”

Regulation of VEGF-A expression and VEGF-A-targeted therapy in malignant tumors

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