Phase I Trial Of Intrahepatic Infusion Of 2nd Generation Designer T Cells For Cea-Expressing Liver Metastases
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the safety of modified T cells delivered into the hepatic artery by documenting the type and severity of any side effects and establishing the Maximum Tolerated Dose (MTD).
Steven C Katz, MD
Roger Williams Medical Center
United States: Food and Drug Administration
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