Melief Cornelis J M
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands.
ISA Pharmaceuticals, Leiden, Netherlands.
Immunother Adv. 2020 Nov 25;1(1):ltaa005. doi: 10.1093/immadv/ltaa005. eCollection 2021 Jan.
During the last two decades, two main schools of modern immunotherapy have come to the forefront. The chimeric anti-CD20 antibody rituximab that was introduced for the treatment of refractory follicular lymphoma in 1998 was one of the first examples of the school of passive immunotherapy. Subsequently major and ever more costly efforts were spent on the development of blockbuster monotherapies including other monoclonal but also bispecific antibodies of highly defined specificity and subclass, antibody-drug conjugates (ADCs), as well as expanded tumor-infiltrating lymphocytes, chimeric antigen receptor (CAR)-transduced T cells, and TCR-transduced T cells. On the other hand, there is the school that works toward active induction of patient B- or T-cell immunity against antigens of choice, or active tolerance against pathogenic allergens, auto-antigens or allo-antigens. Stradled in between these two approaches is treatment with blockers of T cell checkpoint control, which releases the brakes of T cells that have already responded to antigen. Extensive and detailed insight into the cellular and molecular interactions that regulate specific immune responses is indispensable in order to be able to optimize efficacy and rule out treatment related toxicity. This applies to all types of immunotherapy. Our knowledge of the checks and balances in the immune system is still increasing at an unprecedented pace, fostering ever more effective and specific (combination) immunotherapies and offering a rich harvest of innovative immunotherapies in the years ahead.
在过去二十年中，现代免疫疗法的两大主要流派脱颖而出。1998年推出的用于治疗难治性滤泡性淋巴瘤的嵌合抗CD20抗体利妥昔单抗是被动免疫疗法流派的首批实例之一。随后，人们投入了大量且成本不断增加的努力来开发重磅单药疗法，包括其他单克隆抗体以及具有高度明确特异性和亚类的双特异性抗体、抗体药物偶联物（ADC），还有扩增的肿瘤浸润淋巴细胞、嵌合抗原受体（CAR）转导的T细胞和TCR转导的T细胞。另一方面，还有一派致力于主动诱导患者的B细胞或T细胞针对选定抗原产生免疫，或对致病性过敏原、自身抗原或同种异体抗原产生主动耐受。介于这两种方法之间的是使用T细胞检查点控制阻滞剂进行治疗，这种治疗可以解除已经对抗原作出反应的T细胞的制动。为了能够优化疗效并排除治疗相关毒性，深入而详细地了解调节特异性免疫反应的细胞和分子相互作用是必不可少的。这适用于所有类型的免疫疗法。我们对免疫系统中制衡机制的了解仍以前所未有的速度在增加，这促进了更有效、更具特异性的（联合）免疫疗法的发展，并在未来几年带来丰富的创新免疫疗法成果。
