NCT01373047

CEA-Expressing Liver Metastases Safety Study of Intrahepatic Infusions of Anti-CEA Designer T Cells

Phase I Trial Of Intrahepatic Infusion Of 2nd Generation Designer T Cells For Cea-Expressing Liver Metastases

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Roger Williams Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to collect data on the safety and potential effectiveness of 2nd generation designer T cells delivered into the hepatic circulation in patients with liver metastases expressing the CEA tumor marker. Designer T cells are prepared by collecting white blood cells from the participant, and then modifying these cells in the laboratory so that they recognize the tumor antigen, CEA. These modified cells are then given back into the participant so that they can attack and kill tumor cells. The investigators hypothesize that regional delivery of the designer T cells directly into the hepatic artery will minimize systemic toxicity and optimize the changes for therapeutic effect.

Detailed description

T cells have the power to destroy malignant cells under certain conditions, as demonstrated by the rare spontaneous remissions of cancer. However, the endogenous T cell response to cancer fails in the vast majority of patients and the tolerogenic conditions within the liver may pose additional immunologic barriers for those with intrahepatic metastases. The investigators modify patient T cells to kill malignant cells based on their expression of tumor antigens using antibody-defined recognition. The investigators will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors to yield "designer T cells" from normal patient cells. Prior studies in model systems demonstrated that recombinant IgCD28TCR could direct modified T cells to respond to antigen targets with IL2 secretion, cellular proliferation, and cytotoxicity - the hallmarks of an effective, self-sustaining immune response. The present trial will test the regional infusion of anti-CEA designer T cells, given via the hepatic artery using a percutaneous approach. This is an intra-patient dose escalation trial, where patients will receive three doses over the course of six weeks. Doses are 10\^8, 10\^9 and 10\^10 modified T cells. Patients are monitored for safety and response. Patients are on-study for one month after dosing.

Conditions

• Liver Metastases

Interventions

Type	Name	Description
BIOLOGICAL	anti-CEA 2nd generation designer T cells	Three infusions of gene-modified T cells over the course of 6 weeks into the hepatic artery via a percutaneous approach.

Timeline

• Start date: 2011-06-01
• Primary completion: 2013-07-01
• Completion: 2013-07-01
• First posted: 2011-06-14
• Last updated: 2013-07-30

Locations

1 site across 1 country: United States