Abstract

Ciapponi L, Maione D, Scoumanne A, Costa P, Hansen MB, Svenson M, Bendtzen K, Alonzi T, Paonessa G, Cortese R, Ciliberto G, Savino R. Induction of interleukin-6 (IL-6) autoantibodies through vaccination with an engineered IL-6 receptor antagonist. Nature Biotechnology 1997; 15:997-1002.

neutralisation of cytokine activity by monoclonal antibodies or receptor antagonists is beneficial in the treatment of immune and neoplastic diseases, but the necessity for continuous parenteral delivery of these anticytokine agents poses considerable practical limitations. A viable alternative is to induce a neutralising antibody response. Using transgenic mice with high circulating levels of human interleukin-6 (hIL-6), we show that injection of the hIL-6 receptor antagonist Sant1 (an IL-6 variant with seven amino-acid substitutions) induces a strong anti-hIL-6 antibody response. The elicited antibodies bind circulating hIL-6 with very high affinity, totally masking it, and neutralise hIL-6 bioactivity both in vitro and in vivo.