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

Status: Recruiting
Location: See location...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

TIL from tumor tissue of advanced colorectal cancer patients were cultured, modified and expanded in vitro, and then transfused back to the patients after quality control. The safety and efficacy of the treatment were investigated. The fundamental cause of oncogenesis lies in the accumulation of gene mutations. A large number of gene mutations in tumor cells lead to changes in the encoded amino acid sequence, resulting in the production of tumor-specific proteins. Human T cells recognize tumor-specific peptides (tumor neoantigens) that are presented on the MHC molecules on the surface of tumor cells, leading to T cell enrichment within the tumor. However, due to the immunosuppressive effect of tumors through various ways, the enriched T cells in tumors cannot effectively kill tumor cells. One of the most common examples is that tumors up-regulate the expression of immune checkpoint protein PD-L1, which binds to PD-1 on the surface of T cells and inhibits T cell function. Therefore, in this study, we will obtain tumor tissue via surgery resection or biopsy, and then isolate TIL cells in the tumor under GMP conditions, and further use gene editing technology to knockout PD-1, the obtained gene-edited T cells will have the characteristics of specific recognition of tumor cells, but not sensitive to the immunosuppressive function of tumor cells, so as to achieve the therapeutic effect on tumor patients.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 70
Healthy Volunteers: f
View:

• Patients with advanced colorectal cancer confirmed by histology or cytology, who were not eligible to standard treatment at this stage.

• Patients volunteered to receive surgery or biopsy to obtain tumor tissue for TILs preparation.

• Aged ≥18 and ≤70 years old.

• At least one tumor lesion that could be evaluated according to RECIST, version 1.1.

• ECOG score was 0 or 1.

• Adequate bone marrow and organ function.

• The expected survival time of the enrolled patients was no less than 6 months.

Locations
Other Locations
China
Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
RECRUITING
Shanghai
Time Frame
Start Date: 2024-12-31
Estimated Completion Date: 2026-12
Participants
Target number of participants: 29
Treatments
Experimental: Group A: Low dose
The dose of 5×10\^8 PD-1 edited TILs per kg body weight will be transfused to 3 enrolled cases. If none of the 3 patients showed dose-limiting toxicity, the study would be proceeded and the dose would be escalated for group B. If one patient developed dose-limiting toxicity (DLT), another 3 patients with the same dose of group A would be added for expanded investigation. If there was lower than 1/6 of the patients in group A developed DLT, the study would be proceeded and the dose would be escalated for group B.
Experimental: Group B: Middle dose
The dose of 1×10\^9 PD-1 edited TILs per kg body weight will be transfused to 3 enrolled cases. If none of the 3 patients showed dose-limiting toxicity, the study would be proceeded and the dose would be escalated for group C. If one patient developed DLT, another 3 patients with the same dose of group B would be added for expanded investigation. If there was lower than 1/6 of the patients in group B developed DLT, the study would be proceeded and the dose would be escalated for group C. If there was more than 2/6 of the patients in group B developed DLT, the study would be proceeded with the dose would be dropped for group A.
Experimental: Group C: High dose
The dose of 2×10\^9 PD-1 edited TILs per kg body weight will be transfused to 3 enrolled cases. If none of the 3 patients showed dose-limiting toxicity, the study would be proceeded for group D. If one patient developed DLT, another 3 patients with the same dose of group C would be added for expanded investigation. If there was more than 2/6 of the patients in group B developed DLT, the study would be proceeded with the dose would be dropped for group B.
Experimental: Group D: Expanded investigation
The highest dose of TILs without side effects in groups A, B and C would be transfused. In the case that there were no DLT in group A, B and C, there were total 11 cases in group D.
Related Therapeutic Areas
Sponsors
Leads: Ruijin Hospital

This content was sourced from clinicaltrials.gov

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