Randomized phase-1 trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis

Antigen-specific regulation of autoimmune disease is a major clinical research goal. In seropositive rheumatoid arthritis (RA), T cells help to autoreactive B cells matures the citrullinated antigen-specific immune response, generating RA-specific V-domain glycosylated anti-citrullinated (Cit) protein antibodies (VDG ACPA) before arthritis onset. Repeated low or escalating antigen doses administered under “sub-immunogenic” conditions generally favors tolerance. The aims of this study were to explore the safety, pharmacokinetics, immunological and clinical effects of s.c. DEN-181, comprising liposomes encapsulating self-peptide collagen II259-273 (CII) and NF-KB inhibitor 1,25-dihydroxycholecalciferol (calcitriol) Overall design: scRNA-seq and scTCR-seq of CD45+ immune cells flow-sorted from PBMC of 4 participants in the clinical trial at day1 baseline and 28 days post-dosing (n=1 per dose level including placebo)