Safety of intradermal injection of monosodium urate crystals as a vaccine carrier in volunteers

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.