双特异性抗体介导的血液恶性肿瘤免疫治疗研究进展

Current status of bispecific antibody-mediated immunotherapy for hematologic malignancies

癌症的免疫治疗研究近年来进展显著,通过将双特异性抗体(双抗)桥接、重定向并激活免疫效应细胞杀伤癌细胞,实现了令人瞩目的疗效。自2014年抗-CD19及抗-CD3的双抗blinatumomab获得美国FDA批准用于急性淋巴细胞白血病的治疗以来,重定向免疫效应细胞的双抗在血液恶性肿瘤的临床前和临床中的研究越来越活跃。本综述针对最常见的淋巴细胞瘤、多发性骨髓瘤和白血病3大血液恶性肿瘤,总结了B淋巴细胞、浆细胞和髓细胞不同的癌细胞抗原靶点双抗的科研和临床应用的进展。为了更好地使临床受益及降低毒副反应,寻找特异性更高的癌细胞抗原,优化抗原抗体结合的亲和力,延长双抗分子的体内半衰期,以及重定向不同种类的免疫效应细胞等研究还在持续地拓展,预期双抗介导的免疫疗法将会不断给血液恶性肿瘤带来突破和契机。

Significant advances have been made in cancer immunotherapy recently,of which,bispecific antibodies(BsAbs),through bridging,redirecting and activating immune effector cells to kill cancer cells,are attracting increasing attention.Since the anti-CD19 and anti-CD3 BsAb,blinatumomab,was approved in 2014 by the FDA for the treatment of acute lymphoblastic leukemia,preclinical and clinical research with immune-cell-redirecting BsAbs have been fast growing in the area of hematologic malignancies.This review summarizes the current scientific and clinical investigation of BsAbs targeting different tumor-associated antigens from B lymphocytes,plasma cells and myeloid cells,covering three most common blood cancers,namely,lymphoma,multiple myeloma and leukemia.Further development for better therapeutic benefits and lower adverse events,are continuously being pursued,in particular,looking for more specific tumor antigens,optimizing antigen-antibody affinities,extending the half-life of BsAbs and redirecting different immune effector cells,whose breakthroughs and opportunities are soon to be delivered for the management of hematologic malignancies.