Therapeutic bispecific antibodies against intracellular tumor antigens

Bispecific antibodies (BsAbs)-based therapeutics have been identified to be one of the most promising immunotherapy strategies. However, their target repertoire is mainly restricted to cell surface antigens rather than intracellular antigens, resulting in a relatively limited scope of applications. Intracellular tumor antigens are identified to account for a large proportion of tumor antigen profiles. Recently, bsAbs that target intracellular oncoproteins have raised much attention, broadening the targeting scope of tumor antigens and improving the efficacy of traditional antibody-based therapeutics. Consequently, this review will focus on this emerging field and discuss related research advances. We introduce the classification, characteristics, and clinical applications of bsAbs, the theoretical basis for targeting intracellular antigens, delivery systems of bsAbs, and the latest preclinical and clinical advances of bsAbs targeting several intracellular oncotargets, including those of cancertestis antigens, differentiation antigens, neoantigens, and other antigens. Moreover, we summarize the limitations of current bsAbs, and propose several potential strategies against immune escape and T cell exhaustion as well as some future perspectives.

Automated summary

Bispecific antibodies (BsAbs) have shown promise as immunotherapy strategies, but have been limited to targeting cell surface antigens. However, recent attention has been focused on BsAbs that target intracellular oncoproteins, broadening the scope of tumor antigen targeting and improving the effectiveness of antibody-based therapies.