Tha aim of this clinical trial is to evaluate safety and tolerability of autologous peripheral blood differentiated and matured adult dendritic cells. Immunogenicity of the prduct(DC-DELAY) will be evaluated also.
Individuals that are carriers of a pathogenic or likely pathogenic germline variant in one of the mismatch repair genes (MLH1, MSH2, MSH6).
Participants must have no evidence of active or previous invasive cancer.
Participants must have endoscopically accessible colon.
Participants must consent to follow the standard of care surveillance with colonoscopy and biopsies every 1-2 years.
Individuals that are carriers of a pathogenic or likely pathogenic germline variant in PMS2.
Individuals with active malignancy or previous malignancy (excluding non-melanoma skin cancer)
Participants who cannot be removed from their baseline medication for the duration of the trial to administer the investigational treatment. This includes the daily use of >100 mg aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX) inhibitors.
Any serious uncontrolled and /or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures.
Single group
Autologous Tolerogenic Dendritic cells
Biological/VaccineAutologous peripheral blood differentiated and matured adult dendritic cells loaded with Frameshift-derived neopeptides (FSDN) (DC-DELAY). Eligible participants will receive six intradermal immunizations of DC-DELAY at week 0, 2, 4, 6, 8 and 10.
Proportion of participants with grade 3-4 related adverse events for 12 months following the first immunization.
To evaluate the safety and tolerability of autologous peripheral blood differentiated and matured adult dendritic cells loaded with frameshift derived neopeptides (DC-DELAY) in LS carriers.
Proportion of participants with specific frameshift-derived neoantigens immune response induced by DC-DELAY as measured in peripheral blood by enzyme-linked immune absorbent spot(ELISpot) assay at week 12.
To evaluate specific frameshift-derived neoantigens immunogenicity of DC-DELAY in LS carriers at week 12. NOTE: Immune response will be defined as T-cell reactivity to at least 1 out of 4 of the pools.
Proportion of participants with early immune response induced by DC-DELAY as measured inperipheral blood by ELISpot assay at week 6.
To evaluate the early-term specific frameshift-derived neoantigens immunogenicity of DC-DELAY in LS carriers at week 6.
Proportion of participants with long term immune response induced by DC-DELAY as measured in peripheral blood by ELISpot assay at months 6, 12 and 24.
To evaluate the long-term specific frameshift-derived neoantigens immunogenicity of DC-DELAY in LS carriers at 6, 12 and 24 months.
Proportion of participants with immune response induced by DC-DELAY as measured in the normal colonic mucosa at month 12.
To evaluate the specific frameshift-derived neoantigens immunogenicity of DC-DELAY in the normal colonic mucosa in LS carriers at month 12.
Proportion of participants with mismatch repair deficient colorectal adenomas, advanced neoplasia and/or carcinoma throughout the study duration.
To evaluate the effect of DC-DELAY in LS carriers at week 12 on the burden of mismatch repair deficient colorectal neoplasia throughout the study duration.
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