Bispecific antibodies(bsAbs)refer to a large family of molecules that recognize two different epitopes or antigens.Although a series of challenges,especially immunogenicity and chain mispairing issues,once hindered th...Bispecific antibodies(bsAbs)refer to a large family of molecules that recognize two different epitopes or antigens.Although a series of challenges,especially immunogenicity and chain mispairing issues,once hindered the development of bsAbs,they have been gradually overcome with the help of rapidly developing technologies in the past 5 decades.In the meantime,an increasing number of bsAb platforms have been designed to satisfy different clinical demands.Currently,numerous preclinical and clinical trials are underway,portraying a promising future for bsAb-based cancer treatment.Nevertheless,bsAb drugs still face enormous challenges in their application as cancer therapeutics,including tumor heterogeneity and mutational burden,intractable tumor microenvironment(TME),insufficient costimulatory signals to activate T cells,the necessity for continuous injection,fatal systemic side effects,and off-target toxicities to adjacent normal cells.Therefore,we provide several strategies as solutions to these issues,which comprise generating multispecific bsAbs,discovering neoantigens,combining bsAbs with other anticancer therapies,exploiting natural killer(NK)-cell-based bsAbs and producing bsAbs in situ.In this review,we mainly discuss previous and current challenges in bsAb development and underscore corresponding strategies,with a brief introduction of several typical bsAb formats.展开更多
文摘Bispecific antibodies(bsAbs)refer to a large family of molecules that recognize two different epitopes or antigens.Although a series of challenges,especially immunogenicity and chain mispairing issues,once hindered the development of bsAbs,they have been gradually overcome with the help of rapidly developing technologies in the past 5 decades.In the meantime,an increasing number of bsAb platforms have been designed to satisfy different clinical demands.Currently,numerous preclinical and clinical trials are underway,portraying a promising future for bsAb-based cancer treatment.Nevertheless,bsAb drugs still face enormous challenges in their application as cancer therapeutics,including tumor heterogeneity and mutational burden,intractable tumor microenvironment(TME),insufficient costimulatory signals to activate T cells,the necessity for continuous injection,fatal systemic side effects,and off-target toxicities to adjacent normal cells.Therefore,we provide several strategies as solutions to these issues,which comprise generating multispecific bsAbs,discovering neoantigens,combining bsAbs with other anticancer therapies,exploiting natural killer(NK)-cell-based bsAbs and producing bsAbs in situ.In this review,we mainly discuss previous and current challenges in bsAb development and underscore corresponding strategies,with a brief introduction of several typical bsAb formats.
