Bispecific Antibodies in Hematologic and Solid Tumors: Current Landscape and Therapeutic Advances

Bispecific antibodies (bsAbs) have emerged as a novel class of therapeutics, offering a dual-targeting strategy to enhance the therapeutic efficacy of monoclonal antibodies, which is often limited by tumor heterogeneity and the occurrence of resistance mechanisms. By simultaneously engaging two distinct antigens or pathways, bsAbs disrupt multiple signaling cascades simultaneously, preventing escape mechanisms and offering a more durable response. Furthermore, they can optimize immune activation, improving immune cell recruitment strategies. In particular, T-cell engager bsAbs facilitate immune cell-mediated tumor destruction by linking T cells to tumor antigens. Instead, dual immune checkpoint inhibitors (CPIs) enhance immune activation by blocking inhibitory signals. Additionally, bsAbs targeting tumor growth factors or receptor tyrosine kinases offer solutions for overcoming drug resistance in solid tumors. Although bsAbs have shown remarkable success in hematologic malignancies, their expansion into solid tumors faces key challenges, including tumor heterogeneity, limited tumor penetration, and the risk of on-target, off-tumor toxicities. Addressing these challenges requires innovative engineering strategies, optimized delivery mechanisms, and careful patient selection to maximize therapeutic benefit while mitigating adverse effects. The efficacy of bsAbs in clinical trials has led to their approval for both hematologic and solid malignancies, with numerous agents in development. Combination strategies with chemotherapy, targeted agents, and immune CPIs could represent a promising strategy to further expand their potential. As research progresses, bsAbs are expected to play a role in reshaping the future of precision oncology, offering more effective and tailored treatment options.