Vaccination with Autologous Dendritic Cells Loaded with Autologous Tumour Homogenate After Curative Resection for Stage IV Colorectal Cancer.

Inclusion Criteria:

1. Patients must have histologically confirmed stage IV colorectal cancer surgicallytreated with radical intent.

2. The autologous surgical specimen must have been collected and sent to the SomaticCell Therapy Lab of Istituto Scientifico Romagnolo per lo Studio e la Cura deiTumori (IRST IRCCS) and must fulfil all the acceptance criteria prescribed by theGood Manufacturing practise (GMP) procedures.

3. The patient must be disease-free, as assessed by CT scan or MRI of the chest,abdomen, pelvis performed within 60 days before enrolment. If the resected lesionshad occurred in other sites, these must be also included in the baseline CT scan andin all the subsequent evaluations.

4. The patient must have recovered (grade 1 or less by CTCAE 4.0) from all the adverseevents related to previous surgery.

5. Age >18 years.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

7. Patient must have acceptable organ function, defined as:

8. Haemoglobin >10 g/dl

9. White blood cells ≥4000/μl.

10. Absolute neutrophil count >1500/μl.

11. Platelets ≥100000/μl.

12. aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) <3 timesthe upper institutional reference level.

13. Total bilirubin <1.5 times the upper institutional reference level.

14. Serum creatinine <1.5 times the upper institutional reference level.

15. Patients aged 70 years or older must have left ventricular ejection fraction notlower than 55% as assessed by echocardiography.

16. Female patients of childbearing potential and all male patients must accept and becompliant with an highly effective contraceptive method (i.e. with a failure rate of <1% per year: double barrier method, one barrier method plus spermicidal,intrauterine device, or oral contraception) from informed consent signature and upto three months after end of study. For this purpose are considered of childbearingpotential all female subjects after puberty unless they are post-menopausal for atleast two years or are surgically sterile. Complete abstinence from sexualintercourses is acceptable if patients' lifestyle guarantees his/her strictcompliance with this prescription in the judgement of the Investigator.

17. The patient is willing and able to give written informed consent for the study.

Exclusion Criteria:

1. Patients with residual disease after surgery. Marginal resection of any lesion inthe absence of clinically evident residual disease is acceptable.

2. Patients who relapsed within 6 months since primary treatment of stage I-IIIcolorectal cancer. If adjuvant chemotherapy had been administered, the term must becomputed since last chemotherapy dose.

3. Patient who completed surgery more than 60 days before study enrolment.

4. History of other neoplastic diseases in the previous 5 years, except basal cellcarcinoma of the skin and in situ carcinoma of the cervix uteri treated withcurative surgery.

5. History of congenital or acquired immunodeficiency, including history of organtransplantation.

6. Any positivity for the serologic markers of hepatitis B virus (HBV) (including atleast anti-HBs antibodies and anti-hepatitis B core (HBc) antibodies), hepatitis Cvirus (HCV), HIV or Treponema pallidum. The serologic tests must have been performedwithin 30 days before any GMP-regulated activity (i.e. surgical resection andleukapheresis). The sole positivity for antibodies against the HBV S antigen (i.e.with all other HBV markers negative) is indicative of previous HBV vaccination andtherefore is acceptable.

7. Female patients who are pregnant or nursing.

8. Patients undergone surgery after preoperatory chemotherapy with a fluoropyrimidineplus oxaliplatin, unless they are not candidate for postoperatory chemotherapy withthe same schedule in the opinion of the Investigator (e.g. for unacceptabletoxicity) or refuse completion of the perioperatory treatment.

9. Participation in another clinical trial with any investigational agent within 30days prior to study screening.

10. Any active inflammatory or autoimmune disease requiring systemic steroids or otherimmunomodulatory agents as detailed in section 6.4, or potentially requiring suchtreatments during the study treatment in the judgement of the Investigator.

11. Any clinical condition that, in the opinion of the Investigator or the TransfusionMedicine specialist, is a contraindication to leukapheresis. In addition, allpatients aged 70 or older must be evaluated by a cardiology specialist before theprocedure to exclude any clinically relevant cardiac condition and any grade 3-4cardiac arrhythmia, even if asymptomatic.

12. Any clinical condition that, in the opinion of the Investigator, contraindicates thesubcutaneous administration of low-dose IL-2 as per protocol (see section 6.2 fordetails).

13. Any uncontrolled serious intercurrent illness including, but not limited to, ongoingor active infection, symptomatic congestive heart failure, unstable angina pectoris,cardiac arrhythmia, or psychiatric illness/social situations potentially impactingpatient safety and compliance in the opinion of the Investigator.

14. Refusal of giving written informed consent.