Safety and Tolerability Study of Gene-Edited PD-1 Knockout Tumor-Infiltrating T Cells for Advanced Colorectal Cancer Treatment

What this Trial Is About

This research aims to evaluate the safety and tolerability of PD-1 gene knockout tumor-infiltrating lymphocytes TILs in patients with advanced colorectal cancer who are not eligible for standard treatments. The study explores how gene mutations in tumors produce specific proteins that T cells can recognize, but tumor cells suppress T cell function through proteins like PD-L1 binding to PD-1. By using gene editing to knock out PD-1 in TILs, researchers hope to enhance T cell ability to target tumor cells despite this suppression. The study involves collecting tumor tissue from patients through surgery or biopsy to isolate TILs under controlled conditions. These TILs undergo gene editing to remove PD-1 and are then expanded in the lab. Patients receive transfusions of these modified TILs at escalating doses, starting from 5x108 cells per kg body weight up to higher doses depending on tolerance. Before transfusion, patients are treated with chemotherapy drugs cyclophosphamide and fludarabine. The study includes dose escalation groups and an expanded investigation group to identify the highest dose without side effects. Participants will be followed for 12 months after TIL transfusion, during which their safety and response to treatment will be closely monitored. Researchers will evaluate treatment tolerance, severe treatment-related complications, tumor size through imaging, tumor biomarkers, circulating tumor DNA, cytokine levels, and the presence and persistence of TILs in blood. The total study duration spans 24 months, covering recruitment through data analysis, with up to 20 patients involved.

Study on the Safety and Tolerability of PD-1 Knockout Tumor-infiltrating T Cells (TILs) in the Treatment of Advanced Colorectal Cancer