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

Abstract

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.

Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs

“…In principle, this procedure does not induce T cells against the target antigen. In a previous study by Van Loon et al, it was shown that this is indeed true for CD8 cells, while a moderate CD4 response was noted [17]. Therefore, we think that a similar response was generated in the dogs in our study.…”

“…Passive targeting of eVim by monoclonal antibody therapy specifically and safely inhibited tumor growth in mouse melanoma and colorectal tumor models [14,15]. In order to induce endogenous antibody responses to self-antigens, we developed a novel conjugate vaccine technology, named iBoost [16,17] (Figure S1). Using iBoost vaccinations against eVim in mouse melanoma and colorectal carcinoma models, we observed potent anti-tumor responses characterized by reduced tumor growth, diminished tumor blood vessel density and a more favorable intratumoral immune cell composition [14].…”

Extracellular vimentin as a modulator of the immune response and an important player during infectious diseases

“…developed a vimentin‐binding compound that efficiently inhibits cancer exosome release and reduces the mobility of cancer cells. In addition, vaccination with a conjugate vaccine targeting eVim has demonstrated significant tumor growth inhibition and decreased vessel density in the B16F10 melanoma tumor model 98 . Notably, in the treatment of dogs with bladder cancer, the use of the eVim‐targeted vaccine CVx1 in combination with meloxicam (a nonsteroidal anti‐inflammatory drug) resulted in nearly double the survival rate compared with a control group treated with carboplatin and piroxicam (another nonsteroidal anti‐inflammatory drug) 99 …”