Dendritic Cell Vaccination in Patients With Lynch Syndrome or Colorectal Cancer With MSI

Objectives: In this Radboud University Nijmegen Medical Centre (RUNMC) initiated study our first objective is to investigate toxicity (safety and feasibility) of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients with an MSI-positive CRC and persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet. The secondary objectives of the study are: * to demonstrate that peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population. * to study the pathological and clinical responses, e.g. disease-free survival, determined according to the standard protocol. Study design: This study is a phase I/II open-label study. Study population: Two groups of adults will be vaccinated: Group I) CRC patients, who are known to carry a germline MMR-gene mutation and patients with an MSI-positive CRC and yet unknown or negative MMR-gene mutation status. Group II) persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet. All participants need to be HLA-A2.1 positive.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* histologically documented evidence of CRC (group I) and Lynch syndrome carrier without signs of disease (group II)
* HLA-A2.1 phenotype is required
* MSI high tumor
* WBC \>3.0 x 109/l, lymphocytes \>0.8 x 109/l, platelets \>100 x 109/l, serum crea¬tinine \<150 µmol/l, serum bilirubin \<25 µmol/l
* WHO performance status 0-1 (Karnofsky 100-70%)
* Age 18-75 years
* Expected adequacy of follow-up
* Written informed consent

Exclusion Criteria:

* History of malignancy in the past 5 years with the exception of adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
* Serious active infections, HbsAg or HIV positive (test only in case of high risk or clinical suspicion)
* Autoimmune diseases or organ allografts
* Concomitant use of immunosuppressive drugs
* Known allergy to shell fish
* Pregnant or lactating women