| First Author | Lin F | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 26 | Pages | 7470-7491.e32 |
| PubMed ID | 39504957 | Mgi Jnum | J:359311 |
| Mgi Id | MGI:7786326 | Doi | 10.1016/j.cell.2024.10.016 |
| Citation | Lin F, et al. (2024) Multimodal targeting chimeras enable integrated immunotherapy leveraging tumor-immune microenvironment. Cell |
| abstractText | Although immunotherapy has revolutionized cancer treatment, its efficacy is affected by multiple factors, particularly those derived from the complexity and heterogeneity of the tumor-immune microenvironment (TIME). Strategies that simultaneously and synergistically engage multiple immune cells in TIME remain highly desirable but challenging. Herein, we report a multimodal and programmable platform that enables the integration of multiple therapeutic modules into single agents for tumor-targeted co-engagement of multiple immune cells within TIME. We developed the triple orthogonal linker (T-Linker) technology to integrate various therapeutic small molecules and biomolecules as multimodal targeting chimeras (Multi-TACs). The EGFR-CD3-PDL1 Multi-TAC facilitated T-dendritic cell co-engagement to target solid tumors with excellent efficacy, as demonstrated in vitro, in several humanized mouse models and in patient-derived tumor models. Furthermore, Multi-TACs were constructed to coordinate T cells with other immune cell types. The highly modular and programmable feature of our Multi-TACs may find broad applications in immunotherapy and beyond. |
