Abstract
We previously reported induction of cytotoxic T cells using monocyte-derived dendritic cells stimulated with complexes of an idiotype from multiple myeloma cells attached to monosodium urate monohydrate (MSU) in vitro. In addition, we have reported translational research that confirmed the safety of intradermal injection of MSU crystals alone to healthy donors. In the present study, we conducted a phase I study to confirm the safety of intradermal injection of idiotype-MSU complexes to myeloma patients. Our target patients were immunoglobulin G-type or Bence Jones-type myeloma patients. We had scheduled three different dosages of idiotype as follows: 0.5 mg (n = 3), 1 mg (n = 3) and 2 mg (n = 3). However, in the end, we injected 0.5 mg of idiotype to 3 patients and 1 mg of idiotype to 2 patients. We observed these patients for 8 weeks. All 5 patients showed grade 1 erythema and 1 patient showed grade 1 liver dysfunction; no patient showed increased uric acid levels, hematological toxicities or renal dysfunction. Thus, we were able to confirm the safety of intradermal injection of idiotype-MSU complexes. However, none of the 5 patients achieved complete response or partial response during the observation period; therefore, we discontinued this study. A functional deficiency in circulating dendritic cells or a lower immunogenicity of autologous idiotype proteins has been reported in multiple myeloma patients. We will continue to search for another disease with a tumor antigen that can be attached to MSU crystals.
