In this study our primary objective is to induce or enhance an immune response to tumor antigens in Lynch syndrome mutation carriers (with and without colorectal adenomas or carcinomas) and patients with sporadic colorectal cancer (CRC) showing microsatellite instability (MSI-high), the hallmark of MMR dysfunction, and test the hypothesis that DC vaccination might be effective as prophylactic treatment in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Lynch syndrome mutation carriers.
Conditions
Interventions
Product Name: Peptide-loaded Dendritic cell product
Pharmaceutical Form: Solution for injection
Sponsors
Radboud University Nijmegen Medical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
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 >3.0×109/l, lymphocytes >0.8×109/l, platelets >100×109/l, serum crea¬tinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to investigate the safety and feasibility of vaccination with frameshift-derived neoantigen-loaded DC.;Secondary Objective: The secondary objectives of the study are to evaluate whether peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population and the pathological and or clinical responses, e.g. disease-free survival, determined according to the standard protocol. ;Primary end point(s): The first objective of this study is to evaluate safety and feasibility of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients, who group I: are known to carry a germline MMR-gene mutation (Lynch syndrome patients) and patients with an MSI-positive CRC and yet unknown of negative MMR-gene mutation status and group II: persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet. | — |
Countries
Netherlands
Outcome results
None listed