Advancing immunotherapy via multiple immune cells co-engagement

Immunotherapy has demonstrated remarkable clinical success in a wide range of malignancies, owing to its high specificity and durable therapeutic effects. However, its efficacy is constrained by multiple factors arising from the complex and heterogeneous tumor microenvironment (TME). Strategies capable of simultaneously and synergistically engaging multiple immune cells in TME represents a promising yet challenging frontier. Here we begin with a brief overview of current immune cell engagers harnessing the single immune cell types, such as T, NK cells and other immune cells. We then focus on the next generation of multiple immune cell-type co-engagement immunotherapies, discussing their targets, mechanisms, and therapeutic design. This review outlines both opportunities and hurdles of the multiple immune cell co-engagers, paving the way for more effective antitumor modalities.