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.
A single-centre, single-arm phase I/II clinical trial evaluating the safety and feasibility of therapeutic multi-epitope vaccination targeting emergent cancer neoantigens for tumour prevention. The study will include LS subjects aged 35-75 who carry a confirmed germline MMR gene mutation (MLH1, MSH2, or MSH6) and have no clinical signs of disease. Participants will be followed for 36 months, with an additional 7 years of follow-up
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
13
Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally (3-7x10\^6 DC)
Radboudumc
Nijmegen, Netherlands
Number of participants successfully enrolled for manufacturing autologous DC product with sufficient yield for at least one injection intranodally (IN) for treatment purposes and one intradermally (ID) for diagnostic purposes(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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