Preventive Dendritic Cell Vaccination for Lynch Syndrome

NCT07412197 | Not Yet Recruiting Phase 1

• 1 other identifier: EU CT 2025-524046-10-00
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lynch Syndrome

Keywords

Dendritic cells; Cancer vaccine; Hereditary cancer; Lynch Syndrome; Prevention; Neoantigens

Outcome Measures

Primary Outcomes (2)

• 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

• Number of participants with Treatment-Related adverse events as assessed by CTCAE v5.0 (Safety)

  2 years

Secondary Outcomes (3)

• To assess whether neoantigen-specific T cells are induced by the DC vaccine (immunogenicity).

  4 years

• Disease-free survival

  10 years

• Quality of Life Questionnaires

  baseline, week 3, week 28, week 50, month 36, month 60, month 84, month 108

Study Arms (1)

DC vaccination

EXPERIMENTAL

Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally

Biological: DC vaccination

Interventions

DC vaccination BIOLOGICAL

Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally (3-7x10\^6 DC)

DC vaccination

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Dutch Cancer Society: collaborator

Study Sites (1)

Radboudumc

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 17, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): June 1, 2036
• Last Updated: May 6, 2026

Record last verified: 2025-12

Locations

NL (1)