Anti-CD19 monoclonal antibody, clone NC20-2

Introduction Evidence-based treatment options for neuromyelitis optica spectrum disorders (NMOSD) patients are beginning to enter the market. Where previously, there was only the exclusive use of empiric and off-label immunosuppressants in this rare and devastating central nervous system autoimmune disease. Areas covered In accordance to expanding pathogenetic insights, drugs in phase II and III clinical trials are presented in the context of the current treatment situation for acute attacks and immunopreventative strategies in NMOSD. Some such drugs are the 2019-approved complement inhibitor eculizumab, other compounds in late development include its modified successor ravulizumab, IL-6 receptor antibody satralizumab, CD19 targeting antibody inebilizumab and the TACI-Fc fusion protein telitacicept. Expert opinion Moving from broad immunosuppression to tailored treatment strategies, the prospects for efficient NMOSD therapy are positive. For the first time in this disease, class I treatment evidence is available, but long-term data will be necessary to confirm the overall promising study results of the compounds close to approval. While drug development still centers around AQP4 antibody seropositive patients, current and future research requires consideration of possible diverging treatment demands for the smaller group of seronegative patients and patients with presence of MOG antibodies.

BACKGROUND. Preclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (modified immune cells [MICs]), induced long-term specific immunosuppression against the allogeneic donor. METHODS. In this phase I trial, patients received either 1.5 x 10(6) MICs per kg BW on day -2 (n = 3, group A), or 1.5 x 10(8) MICs per kg BW on day -2 (n = 3, group B) or day -7 (n = 4, group C) before living donor kidney transplantation in addition to post-transplantation immunosuppression. The primary outcome measure was the frequency of adverse events (AEs) until day 30 (study phase) with follow-up out to day 360. RESULTS. MIC infusions were extremely well tolerated. During the study phase, 10 treated patients experienced a total of 69 AEs that were unlikely to be related or not related to MIC infusion. No donor-specific human leukocyte antigen Abs or rejection episodes were noted, even though the patients received up to 1.3 x 10(10) donor mononuclear cells before transplantation. Group C patients with low immunosuppression during follow-up showed no in vitro reactivity against stimulatory donor blood cells on day 360, whereas reactivity against third-party cells was still preserved. Frequencies of CD19(+)CD24(hi)CD38(hi) transitional B lymphocytes (Bregs) increased from a median of 6% before MIC infusion to 20% on day 180, which was 19- and 68-fold higher, respectively, than in 2 independent cohorts of transplanted controls. The majority of Bregs produced the immunosuppressive cytokine IL-10. MIC-treated patients showed the Immune Tolerance Network operational tolerance signature. CONCLUSION. MIC administration was safe and could be a future tool for the targeted induction of tolerogenic Bregs.