Preventive Dendritic Cell Vaccination for Lynch Syndrome (PREVENT-Lynch)

Targeting Cancer Neoantigens Through Multi-Epitope Vaccination for Tumour Prevention in Lynch Syndrome: a Phase I/II Clinical Trial.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Lynch Syndrome
• Intervention / Treatment: Biological: DC vaccination

Detailed Description

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
• Enrollment (Estimated): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboudumc
    • Contact: Jolanda de Vries, Prof. dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• a confirmed gPV in MLH1 or MSH2 and without a prior history of MMR-D cancer.
• a confirmed gPV in MSH6, whether or not they have a history of MMR-D cancer. MSH6 subjects with a history of MMR-D cancer have to be cancer-free for more than 1 year.
• previous surgical treatment may include any resection up to and including hemicolectomy; subjects who have undergone (sub)total colectomy are excluded due to the substantially reduced risk of cancer occurrence.
• aged between 35 and 75 for subjects with gPV in MLH1 and MSH2; and aged between 40 and 75 for subjects with gPV in MSH6.
• Lynch syndrome subjects without clinical signs of disease.
• Lynch syndrome subjects with a prior history of colorectal premalignancies with at least 1 adenoma sample archived.
• Lynch syndrome subjects without prior treatment for LS-associated cancer, except for MSH6 subjects who are >1 year disease-free and whose prior surgical treatment did not include subtotal colectomy.
• Routine surveillance colonoscopy must be performed within 16 weeks prior to start of study, to exclude (pre)malignancy.
• HLA-A02.01 genotype
• Adequate hematologic, renal, and liver function as defined by laboratory values: WBC >3.0^109/l, lymphocytes >0.8^109/l, platelets >100^109/l, haemoglobin >7,0 mmol/l (9.0 g/dl), estimated glomerular filtration rate > 45 ml/min/1.73m2, AST/ALT <3 x ULN, serum crea¬tinine <150 µmol/l, serum bilirubin <1.5 x ULN (exception: Gilbert's syndrome is permitted).
• WHO performance status of 0 or 1
• No concomitant use of immunosuppressive drugs orally or intravenously. Topical and intranasal steroids are permitted.
• No uncontrolled infectious disease, i.e., negative testing for HIV, Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and syphilis (Treponema Pallidum Hemagglutination Assay (TPHA)).
• No autoimmune disease such as, but not limited to, inflammatory bowel disease, multiple sclerosis, and lupus. Subjects with type 1 diabetes mellitus, hypothyroidism after autoimmune thyroiditis and skin disorders are not excluded.
• No serious (bleeding and clotting) condition that may interfere with safe leukapheresis.
• No pregnant or lactating women. hCG tests will be performed regularly during the trial to confirm absence of pregnancy.
• No Women Of Child-Bearing Potential (WOCBP) or male partners of WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for up to 8 weeks after the last administration of the treatment. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea > 12 consecutive months].
• Subjects must have absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions must be discussed with the subject before registration in the trial.
• Expected adequacy of follow-up.
• Written informed consent.

Exclusion Criteria:

• Individuals with a history of malignancy in the past. Allowed malignancies are adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, carcinoma in situ (e.g., DCIS/LCIS/cervical CIS), papillary thyroid carcinoma, and low-risk prostate carcinoma; all locally resected with negative surgical margins and not treated with systemic therapy.
• Organ allografts.
• Known allergy to shellfish.
• Inability to understand and communicate in Dutch.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DC vaccination; Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally	Biological: DC vaccination; Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally (3-7x10^6 DC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with Treatment-Related adverse events as assessed by CTCAE v5.0 (Safety)	2 years
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)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	baseline, week 3, week 28, week 50, month 36, month 60, month 84, month 108

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Dutch Cancer Society

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): June 1, 2036

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Prevention; Cancer vaccine; Dendritic cells; Hereditary cancer; Lynch Syndrome; Neoantigens
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Genetic Diseases, Inborn; Metabolic Diseases; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Colorectal Neoplasms, Hereditary Nonpolyposis
• Other Study ID Numbers: EU CT 2025-524046-10-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No