Immune cell engagers in lung cancer

In recent years, significant progress has been made in lung cancer treatment paradigms with the continuous unraveling of the tumor microenvironment and the ongoing advancement of immunotherapy. As an emerging immunotherapy modality, Immune Cell Engagers (ICEs) aim to effectively mobilize the body’s antitumor immune response by targeting tumors and activating immune effector cells such as T cells, NK cells, and myeloid cells. Recent studies have indicated that T-cell engagers (TCEs), exemplified by bispecific T-cell engagers (BiTEs), can enhance T-cell immunological activity within the lung cancer microenvironment and demonstrate significant antitumor effects in both in vitro and in vivo experiments. However, the highly heterogeneous nature of the lung cancer microenvironment and its complex immunosuppressive networks limit the therapeutic efficacy of ICEs. Meanwhile, key challenges remain in improving target cell specificity, lowering toxicity to non-target cells, and optimizing pharmacokinetics. This review systematically summarizes the mechanisms of action and recent advances of ICEs in lung cancer immunotherapy, explores innovative development directions for next-generation ICEs, and highlights their significant potential in driving paradigm shifts in lung cancer immunotherapy.