Induction of Specific T Cell Responses in Colorectal Cancer Patients With Liver Metastases Upon Vaccination With Autologous Dendritic Cells Pulsed With CEA-peptide or Electroporated With CEA-RNA: Evaluation of in Vivo Immune Response.
For arm A and B
1. Histological documented evidence of colorectal cancer.
2. Primary tumor surgically removed, recurrence(s) in the liver.
3. Planned surgical excision of liver metastases.
4. HLA-A2.1 phenotype according to lymphocyte HLA typing.
5. Expression of CEA on primary tumor.
6. ECOG performance status 0-1, life expectancy > 3 months.
7. Age 18-75 years.
8. WBC > 3.0 x 109/l, lymphocytes > 0.8 x 109/l, platelets > 100 x 109/l, serum
creatinine < 150 μmol/l, serum bilirubin < 25 μmol/l.
9. Expected adequacy of follow-up.
10. Written informed consent.
1. Clinical signs of extra hepatic metastases, in patients with a clinical suspicion of
other metastases diagnostic tests should be performed to exclude this.
2. Prior chemotherapy, immunotherapy, or radiotherapy within three months before planned
surgical excision is allowed.
3. A history of myocardial infarction, angina pectoris, cardiac arrhythmias,
cerebrovascular accidents, transient ischemic attacks or severe hypertension
(exclusion criteria for autologous blood donation)
4. Concomitant use of corticosteroids or other immunosuppressive agents.
5. A history of any second malignancy in the past five years excluding adequately
treated basal carcinoma of skin or carcinoma in situ of cervix.
6. Serious concomitant disease, active infections. Specifically, patients with
autoimmune disease or organ allografts and patients with a history of HBsAg or HIV
7. A known allergy to shell fish.
8. Pregnant or lactating women.
For arm C (side-study)
1. histological proof of colorectal cancer
2. HLA-A0201 positive
3. stage III (T1-4N1-2M0) cancer or high risk stage II (T4 and/or poor
differentiation in histology and/or perforation and/or obstruction and/or venous
invasion and/or histological analysis of ≤10 lymph nodes)
4. ≤ 8 weeks since surgical resection of primary colorectal tumor
5. Age 18-75 years
6. WHO performance 0-1 (Karnofsky 100-70%)
7. WBC ≥ 3.0x109/l
8. Platelets ≥ 100x109/l
9. Hb ≥ 6 mmol/l
10. Total bilirubin ≤ 2x UNL
11. ASAT and ALAT ≤ 3x UNL
12. Serum creatinine ≤ 1.5 x UNL
13. Expected adequacy of follow-up
14. Signed written informed consent
1. A history of second malignancy within the last 5 years. Adequately treated basal
carcino¬ma of skin or carcinoma in situ of cervix is acceptable within this period
2. Serious concomitant disease. Autoimmune disease or organ grafts.
3. Other serious concomitant diseases preventing the safe administration of study drugs
or likely to interfere with the study assessments.
4. A known allergy to shell fish (contains KLH)
5. Pregnant or lactating women