RATIONALE: Inserting a gene that has been created in the laboratory into a person's white blood cells may make the body build an immune response to kill cancer cells.

PURPOSE: Phase I trial to study the effectiveness of gene therapy in treating patients who have cancer that has not responded to previous therapy.

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.

Patients are followed every 2 weeks for 2 months.

PROJECTED ACCRUAL: A total of 6-9 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven CEA expressing adenocarcinoma

  • Serum CEA levels greater than 10 ng/mL
  • Failed standard therapy

• Measurable disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• 0-2

Life expectancy:

• Greater than 2 months

Hematopoietic:

• Not specified

Hepatic:

• No significant hepatic disease
• Bilirubin no greater than 3 mg/dL
• No active clinical disease caused by hepatitis B

Renal:

• No significant renal disease
• Creatinine no greater than 3 mg/dL

Cardiovascular:

• No significant cardiovascular disease

Pulmonary:

• No significant pulmonary disease

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No significant endocrine, rheumatologic, or allergic disease
• No active clinical disease caused by cytomegalovirus or tuberculosis
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• Not specified