Phase I Study of T Cells Modified With Chimeric AntiCEA Immunoglobulin-T Cell Receptors (IgTCR) in Adenocarcinoma

OBJECTIVES:

• Determine the safety and maximum tolerated dose of T cells activated in vitro and modified with chimeric anti-CEA immunoglobulin T cell receptors (Ig TCR) in patients with CEA expressing adenocarcinoma.
• Determine the pharmacokinetics of this regimen by the persistence of modified T cells in the blood of these patients.
• Evaluate the immunogenicity of murine sequences in chimeric anti-CEA Ig TCR.
• Assess immunologic parameters which correlate with the efficacy of this regimen in these patients.
• Evaluate, in a preliminary manner, the efficacy of this regimen in patients with CEA bearing tumors.

OUTLINE: This is a dose escalation study.

Peripheral blood lymphocytes (PBL) are harvested. PBL are activated in vitro and then modified with recombinant chimeric anti-CEA immunoglobulin T cell receptors (Ig TCR). Ig TCR modified T cells are reinfused over 30-60 minutes.

The estimated maximum tolerated dose (MTD) is defined as the dose at which 2 of 6 patients experience unacceptable toxicity. If the MTD is not reached within the first cohort, a second cohort of 3 patients then receives 4 doses of modified T cells at a higher dose.