The aim of this study is to assess safety, feasibility and immunogenicity of vaccination with neopeptide-loaded dendritic cells in Lynch Syndrome subjects who are known to be carrier of a germline MMR-gene mutation without signs of disease.
This is a single centre, single arm, phase I/II clinical trial to evaluate tumour prevention by targeting emergent cancer neoantigens through therapeutic multi-epitope vaccination in which LS subjects aged 35-75 who are confirmed to carry a germline MMR-gene mutation in MLH1, MSH2 or MSH6 without clinical signs of disease are participating for 36 months with corresponding 7 years follow-up.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
23
Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally (3-6x10\^6 DC)
Radboudumc
Nijmegen, Netherlands
Number of participants successfully enrolled for manufacturing autologous DC product with sufficient yield for one vaccination cycle by the current GMP team using 2 automated isolation/culture devices (Feasibility)
Time frame: 2 years
Number of participants with Treatment-Related adverse events as assessed by CTCAE v5.0 (Safety)
Time frame: 2 years
To assess whether neoantigen-specific T cells are induced by the DC vaccine (immunogenicity).
Immunogenicity will be assessed by the percentage of participants showing a neo-antigen-specific T cell response, defined by the expansion of T cells that recognize tumor antigens and demonstrate effector functions. Non-responders are those with no T cell expansion or insufficient immune activity.
Time frame: 4 years
Disease-free survival
To evaluate whether LS subjects who develop a T cell response to a frameshift-derived neoantigen included in the vaccine have an improved DFS; defined as the time from the 1st vaccination until development of an MMR-D colorectal adenoma, any LS-associated carcinoma in situ, or any LS-associated carcinoma, or until follow up ends, whichever occurs first.
Time frame: 10 years
Quality of Life Questionnaires
To evaluate whether LS subjects who develop a T cell response to a frameshift-derived neoantigen included in the vaccine have an improved QoL; defined as patient's self-perceived physical, psychological and social well-being in relation to their health status, assessed using questionnaires.
Time frame: baseline, week 3, week 28, week 50, month 36, month 60, month 84, month 108
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