单抗类药物的免疫原性问题及其控制

单抗类药物(单克隆抗体药物和受体-Fc融合蛋白药物)近年来在癌症和自身免疫性疾病等领域取得了显著的疗效。根据诱发的抗药物抗体的类型不同,单抗类药物的免疫原性可能导致不同的临床后果,直至影响单抗类药物的有效性和安全性。单抗类药物免疫原性的发生机制尚没有明确的定论,可能与多种因素有关,其中蛋白质多聚体对免疫原性有显著影响。根据"质量源于设计"的原则,从单抗类药物的分子设计和工艺设计出发,采取人源化改造、开发人类抗体、检测和控制产品中多聚体含量等,有助于降低单抗类药物的免疫原性,实现单抗类药物的有效性、安全性和可生产性之间的平衡。

The Immunogenicity and Control of Therapeutic Monoclonal Antibodies

Therapeutic monoclonal antibodies and receptor-Fc fusion proteins have exhibited excellent efficacy in the treatment of cancer and autoimmune diseases. The immunogenicity of these biotherapeutics may impact their safety and efficacy profile, depending on the nature of the anti-drug antibodies elicited. The exact mechanism of such immunogenicity is unclear, however, it is associated with many different inherent and external conditions. Protein aggregates have been known contributing to immunogenicity. Rational design of molecular sequence and production process under the guidance of Quality by Design, including the development of humanized antibody and fully human antibody, and quantification and control of protein aggregates of the drug product, will help to reduce or eliminate immunogenicity and keep the balance between efficacy, safety and manufacturability of such biotherapeutics.