A Phase I Study of Regulatory T Cell Depletion With Denileukin Diftitox Followed by Active Immunotherapy With Autologous Dendritic Cells Infected With CEA-6D Expressing Fowlpox-Tricom in Patients With Advanced or Metastatic Malignancies Expressing CEA

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed malignancy

- Metastatic disease

- Tumor expresses carcinoembryonic antigen (CEA), as evidenced by any of the following:

- At least 50% of tumor expresses CEA by immunohistochemistry (IHC) with ≥ a
moderate intensity of staining

- Peripheral blood CEA level > 5.0 ng/mL

- Tumor known to be universally CEA-positive (e.g., colon or rectal cancer)

- Measurable or evaluable disease

- Received or refused prior therapy with a possible survival or palliative benefit AND
meets the following disease-specific criteria:

- Patients with colorectal cancer must have experienced disease progression during
≥ 1 prior palliative chemotherapy regimen for metastatic disease comprising 1 of
the following regimens:

- Fluorouracil or capecitabine AND oxaliplatin

- Fluorouracil or capecitabine AND irinotecan

- Chemotherapy in combination with bevacizumab

- Patients with breast cancer must have experienced disease progression during ≥ 1
prior palliative chemotherapy regimen for metastatic disease comprising 1 of the
following regimens:

- Anthracycline- or taxane-based chemotherapy

- Chemotherapy AND trastuzumab (Herceptin®) (required for patients with
tumors overexpressing HER2/neu (i.e., 3+ by IHC or positive by fluorescence
in situ hybridization [FISH])

- Patients with lung cancer must have experienced disease progression during ≥ 1
prior palliative chemotherapy regimen for metastatic disease comprising 1 of the
following regimens:

- Platinum-based (e.g., cisplatin or carboplatin) chemotherapy (for
chemotherapy-naive patients only)

- Taxane-based (e.g., docetaxel or paclitaxel) chemotherapy OR vinorelbine
(for patients who received prior chemotherapy)

- Patients with pancreatic cancer must have experienced disease progression during
prior chemotherapy, including gemcitabine

- Patients with other malignancies must have experienced disease progression after
prior first-line therapy that would confer a survival or palliative benefit, if
such a therapy exists

- Patients who experienced disease progression during prior first-line
palliative chemotherapy must be advised regarding second-line therapy
before study enrollment

- Previously resected brain metastases allowed provided there is no evidence of brain
metastasis within the past month by MRI or CT scan

- No requirement for further systemic chemotherapy for ≥ 3 months

- Hormone receptor status:

- Not specified

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Male or female

Menopausal status

- Not specified

Performance status

- Karnofsky 70-100%

Life expectancy

- More than 6 months

Hematopoietic

- WBC ≥ 3,000/mm^3

- Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed)

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin < 1.5 mg/dL (≤ 2.0 mg/dL for patients with Gilbert's syndrome)

- SGOT and SGPT < 1.5 times upper limit of normal

- Albumin ≥ 3.0 g/dL

- No active acute or chronic viral hepatitis

- Hepatitis B surface antigen negative

- Hepatitis C negative

- No other hepatic disease that would preclude study treatment

Renal

- Creatinine < 1.5 mg/dL

- No active acute or chronic urinary tract infection

Cardiovascular

- No New York Heart Association class III-IV cardiac disease

Immunologic

- HIV negative

- No history of autoimmune disease*, including, but not limited to, the following:

- Inflammatory bowel disease

- Systemic lupus erythematosus

- Ankylosing spondylitis

- Scleroderma

- Multiple sclerosis

- No active cytomegalovirus (CMV) disease

- Patients with CMV-seropositivity are eligible

- No other active acute or chronic infection

- No history of allergies to eggs or any component of the study vaccine, denileukin
diftitox, or diphtheria toxin NOTE: *Patients with a positive anti-nuclear antibody
(ANA) ≤ 1:256 with no other evidence of autoimmune disease are eligible

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 months after
completion of study treatment

- No acute or chronic skin disorder that would preclude study treatment

- No other malignancy within the past 5 years except nonmelanoma skin cancer,
controlled carcinoma in situ of the cervix, or controlled superficial bladder cancer

- No psychological or medical impediment that would preclude study compliance

- No other serious acute or chronic illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- Prior vaccine, dendritic cell, or CEA-targeted immunotherapy allowed

- At least 4 weeks since prior and no other concurrent immunotherapy

- Concurrent palliative single-agent trastuzumab for breast cancer allowed provided
patient has been on therapy for ≥ 3 months before study entry

Chemotherapy

- See Disease Characteristics

- At least 4 weeks since prior and no concurrent chemotherapy

Endocrine therapy

- At least 4 weeks since prior hormonal therapy

- At least 6 weeks since prior steroid therapy except steroids used as premedication
for chemotherapy or contrast-enhanced studies

- No concurrent steroids, including corticosteroids administered to manage toxic
effects from dendritic cell or denileukin diftitox administration

- Concurrent palliative endocrine therapy for breast cancer allowed provided patient
has been on therapy for ≥ 3 months before study entry

Radiotherapy

- At least 4 weeks since prior and no concurrent radiotherapy

Surgery

- See Disease Characteristics

Other

- Recovered from all prior therapy

- At least 4 weeks since prior investigational drugs or procedures

- At least 4 weeks since other prior therapy

- No other concurrent immunosuppressive therapy (e.g., azathioprine or cyclosporine)