Bispecific antibodies in NSCLC: immune reengineering to neutralize adaptive tumor resistance

Over the past few decades, the emergence of immunotherapy and single-target drugs has brought new promise to the treatment of non-small cell lung cancer (NSCLC). Yet the high heterogeneity of NSCLC leads to both primary and acquired resistance that neither sequential monotherapy nor empirical combinations can effectively overcome. In contrast to the conventional coadministration of two separate monoclonal antibodies, bispecific antibodies (BsAbs) feature a series of molecular engineering designs that confer inherent synergistic antitumor effects. We propose that a network pharmacology perspective can be adopted to understand the application of BsAbs in NSCLC and to guide their subsequent development.