Fig. 9

Current and future strategies of ACT in cancer treatment. Currently, adoptive cell therapy is still in its first generation and mainly relies on gene transduction technology to make certain immune cells express receptors that recognize tumor-associated antigens to kill tumor cells. Although many achievements have been made, single engineered immune cells face some challenges, such as poor persistence in vivo, antigen escape, and unpredictable side effects, indicating that adoptive cell therapy needs to be further developed. The second-generation adoptive cell therapy, which simply combines two types of CAR-engineered immune cells, has been preliminarily attempted and has demonstrated better anti-tumor effects. In the next step, we may fully exploit the unique properties of each type of manufactured immune cell, logically combine them to simulate a healthy immune coordination system, and artificially create a positive immune circuit. For example, macrophages and DCs serve as the commander of the immune system, with antigen presentation and a powerful ability to mobilize other immune cells. Combining them with engineered T cells, NK cells, γδT cells, or NKT cells to construct an artificial tumor-specific immune system may better overcome the limitations of current adoptive cell therapy techniques in solid tumors. This is a direction worth considering in the future. Mφ, macrophage; DC, dendritic cell; CostimL, costimulatory ligand; CostimR, costimulatory receptor; and CR, chemokine receptor