Cytokines of the interleukin-17 family are named IL-17A to IL-17F. Correspondingly, the family of their receptors, named IL-17 receptor A to IL-17 receptor E, have also been identified. The IL-17 cytokines bind to their corresponding receptors and thereby mediate different inflammatory responses.
The classical member of the family is IL-17A. Lymphocytes that migrate to infection or injury sites can secrete IL-17A. IL-17A induces the expression of inflammatory cytokines and chemokines, thereby recruiting additional immune cells to the inflammation site and exacerbating the inflammatory response. In addition, IL-17A induces the expression of some factors relevant to tissue repair, thus accelerating recovery of the organism. Although interleukin-17A has the effect of amplifying the immune defense response and protecting organisms during the process of anti-infection and tissue repair in the host, interleukin-17A is highly expressed in many patients suffering from autoimmune diseases and cancers, and excessive expression of interleukin-17A plays a negative role in pathologic development because it can induce the expression of various inflammatory factors. Many animal experiments have shown that the pathological severity of various autoimmune diseases can be effectively suppressed by interleukin-17A deficiency or interleukin-17A antibody neutralization. There is evidence that IL-17 signaling could be an effective target for treating autoimmune diseases, including rheumatoid arthritis (RA), psoriasis, Crohn's disease, multiple sclerosis (MS), psoriasis disease, asthma and lupus (see, for example, Aggarwal et al., J. Leukoc. Biol, 71 (1): 1-8 (2002); Lubberts et al.).
Human IL-17 is a gene encoding a full-length polypeptide having 155 amino acids. The polypeptide comprises a 19-amino-acid signal sequence and a 132-amino-acid mature region. With a relative molecular weight of 17,000 Da, human IL-17A is a glycoprotein existing in the form of a homodimer or a heterodimer (Spriggs et al, J. Clin. Immunol, 17: 366-369 (1997)). The IL-17F homolog can combine with IL-17A to form an IL-17A/F heterodimer. The amino acid sequence of IL-17F (IL-24, ML-1) has up to 55% similarity to that of IL-17A, and both have the same receptor, IL-17R. IL-17R is ubiquitously expressed in a variety of cells, including vascular endothelial cells, peripheral T cells, B cells, fibroblasts, myelomonocytes and bone marrow stromal cells (Kolls et al, Immunity, 21: 467-476 (2004); Kawaguchi et al, J. Allergy Clin. Immunol, 114 (6): 1267-1273 (2004); Moseley et al, Cytokine Growth Factor Rev, 14 (2): 155-174 (2003)).
From the discovery of interleukin-17A, until now, a variety of anti-IL-17A antibodies have been identified, such as CN101001645A, CN101326195A, CN101646690A, but there is still a need for the development of various kinds of improved antibodies to effectively reduce or eliminate IL-17 activity in inflammatory responses and autoimmune diseases.