Cancer Vaccination against Extracellular Vimentin Efficiently Adjuvanted with Montanide ISA 720/CpG.

Abstract

Simple SummaryVaccination against specific proteins in the tumor vasculature has already shown promising results in several preclinical studies. However, the efficacy of vaccination highly depends on the adjuvant used. This study aimed to assess the potential use of the biodegradable adjuvant Montanide ISA 720 in combination with our vaccine against extracellular vimentin, a protein specifically secreted by the tumor vasculature. Compared to the potent but toxic Freund’s adjuvant, Montanide showed a comparable immune response and tumor growth inhibition in a preclinical vaccination experiment in mice, especially when supplemented with the immune stimulatory molecule CpG. We also observed that vaccination reduced the blood vessel count and increased the infiltration of immune cells. We conclude that Montanide ISA 720 shows potential to be used as an adjuvant for vaccination against extracellular vimentin for future clinical studies in cancer patients.Extracellular vimentin is a specific marker of the tumor vasculature, where it is secreted by tumor endothelial cells. Vaccination with a conjugate vaccine targeting extracellular vimentin was previously shown to induce a potent humoral immune response and tumor growth inhibition in mice. These data were obtained by vaccination using the toxic Freund’s adjuvant (FA) and are therefore not directly translatable into the clinic. In the present study, we aimed to investigate the potential of the biodegradable Montanide ISA 720 adjuvant. We tested Montanide either alone (MN) or supplemented with CpG 1826 (MN-C). Both adjuvant compositions, as well as FA, resulted in a significant tumor growth inhibition and decreased vessel density in the B16F10 melanoma tumor model. Vaccination of mice with either FA or MN-C resulted in an equally potent humoral immune response towards vimentin, while the antibody titers obtained with MN alone were significantly lower compared to FA. Vaccination coincided with the infiltration of immune cells. The highest number of intratumoral immune cells was seen in tumors from the MN-C group. Therefore, we conclude that Montanide ISA 720 supplemented with CpG allows efficient vaccination against extracellular vimentin, which is a prerequisite for the transfer of the vaccine into the clinic.