Safety of Intradermal Injection of Monosodium Urate Crystals as a Vaccine Carrier in Volunteers

Abstract

Monosodium urate (MSU) crystals are known to induce gouty arthritis, but also evoke specific cell immunity and work as an adjuvant by delivering several kinds of binding proteins, including idiotypic cancer vaccine peptides into dendritic cells. To investigate the potency of MSU crystals as a cancer vaccine carrier in vivo, this preclinical study examined whether intradermal injection of MSU crystals was safe for healthy adults. Subjects comprised 12 volunteers. Four different dose levels of MSU crystals were injected as follows: 2 μg (n = 3), 20 μg (n = 3), 200 μg (n = 3), or 2000 μg (n = 3). At 24 hours after administration, documented erythema was seen around the injection site in a dose-dependent manner, particularly in all adults with MSU dose ≥200 μg. However, redness was limited to the grade I level of the National Cancer Institute toxicity criteria. Serum uric acid levels did not show any change before and after injection. Moreover, neither gouty arthritis nor tophi developed in any volunteers, indicating that intradermal injection of MSU crystals did not induce systemic inflammation at the doses that evoked significant local inflammation. These findings suggest that intradermal injection of MSU crystals is fundamentally safe and should be made available for clinical trials using MSU-crystal-conjugated cancer vaccines.

Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs

“…77 MSU crystals have been shown to be safe after intradermal injection (2-2,000 µg) in humans. 78 They can induce maturation of dendritic cells in intraperitoneally injected mice with ovalbumin resulting in efficient priming of CD8 + T cells. 79 MSU crystals stimulate production of ROS and phagolysosome maturation.…”

Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis

“…In this context, future studies may reveal additional regulatory mechanisms unique to alum that suppress cytolitic T cell induction. Finally, the safety of intradermal injection of MSU in healthy human volunteers has been reported [ 40 ]. Although this latter study was not characterized as a phase 1 clinical trial, it represents a preliminary study showing apparent absence of MSU toxicity in humans and may provide the basis for future controlled clinical trials.…”

IL-1βR-dependent priming of antitumor CD4+T cells and sustained antitumor immunity after peri-tumoral treatment with MSU and mycobacteria

“…MSU has been found to be safe as a vaccine adjuvant for use in humans. 42 Mycobacteria such as Bacillus Calmette-Gu erin are already used in the clinic for the treatment of bladder cancer, 43 and their safety in immune-compromised cancer patients can be further improved by replacing with non-pathogen derived species such as Msmeg 44 or by heatkilling. 16 We conclude that, on the basis of its efficacy and safety profile, MSU C Msmeg would be a useful basis for immune stimulatory treatments, also in combination with other immunotherapies or chemotherapy, to promote and sustain anticancer immunity.…”