Current landscape and future directions of bispecific antibodies in cancer immunotherapy

Abstract

Recent advances in cancer immunotherapy using monoclonal antibodies have dramatically revolutionized the therapeutic strategy against advanced malignancies, inspiring the exploration of various types of therapeutic antibodies. Bispecific antibodies (BsAbs) are recombinant molecules containing two different antigens or epitopes identifying binding domains. Bispecific antibody-based tumor immunotherapy has gained broad potential in preclinical and clinical investigations in a variety of tumor types following regulatory approval of newly developed technologies involving bispecific and multispecific antibodies. Meanwhile, a series of challenges such as antibody immunogenicity, tumor heterogeneity, low response rate, treatment resistance, and systemic adverse effects hinder the application of BsAbs. In this review, we provide insights into the various architecture of BsAbs, focus on BsAbs’ alternative different mechanisms of action and clinical progression, and discuss relevant approaches to overcome existing challenges in BsAbs clinical application.

Radiotherapy and immunology

“…TGF-β can increase the proliferation of Tregs within the TME ( Santarpia et al, 2015 ). TGF-β signaling is required for MDSC migration and suppressive function after IR ( Wang et al, 2022 ). TGF-β signaling triggers the polarization of M2-type macrophages and the differentiation of suppressive monocytes, thereby promoting tumor progression ( Novitskiy et al, 2012 ; Pang et al, 2013 ).…”

Synthesis of site‐specific Fab‐drug conjugates using ADP‐ribosyl cyclases

“…To date, 14 ADCs have received approvals from the United States Food and Drug Administration (FDA) for cancer treatment (Fu et al, 2022; Samantasinghar et al, 2023). Furthermore, numerous ADCs are currently at different stages of preclinical and clinical studies for oncology and other diseases (Drake & Rabuka, 2017; Wei et al, 2022). Conventional ADCs are prepared through random conjugation of payloads with cysteine or lysine residues that may vary in number and/or position across different antibody molecules.…”

Generation of Bispecific Antibodies by Functionalized Poly‐ADP‐Ribose Polymers

“…Simultaneously engaging with two distinct types of antigen molecules, bispecific antibodies possess unique and strong potential for treatment of human diseases, especially in cancer immunotherapy (Li et al., 2020; Wei et al., 2022; Yang et al., 2017). To date, nine bispecific antibodies are approved for clinical use by the FDA, many of which function through recruiting immune effector cells to tumors and activating potent cancer‐specific immunity (Esfandiari et al., 2022; Krishnamurthy & Jimeno, 2018).…”