Autoimmune Neurological Diseases and Those Secondary to Immunotherapy: Study of Immunological Mechanisms and Research Into Targets of Immune Attack (DINAMIC)

Maladies Neurologiques Auto-immunes et Secondaires à l'immunothérapie : étude Des mécanismes Immunologiques et Recherche Des Cibles de l'Attaque Immune

The pathophysiology of neurological toxicities secondary to immune checkpoint inhibitors (ICIs) is unknown. Various mechanisms have been proposed: activation of cytotoxic CD8 T cells, autoantibodies via activation of B cells and CD4 cells, non-specific inflammation through the production of pro-inflammatory cytokines, and complement activation.

The aim of this research is to characterise the pathophysiological mechanisms of neurotoxicities in cancer patients treated with ICIs.

Study Overview

• Status: Not yet recruiting
• Conditions: Neurological Diseases; Auto Immune Disease
• Intervention / Treatment: Other: Lumbar puncture and blood sampling

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, MD PhD; Phone Number: +33 0142499742; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: Stefania Cuzzubbo, MD; Phone Number: +33 0171207467; Email: stefania.cuzzubbo@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult patient (aged ≥ 18 years)
• Affiliated with a social security scheme
• Express consent to participate in the study
• Indication for lumbar puncture And
• Patients with cancer, undergoing treatment with ICIs, presenting neurological symptoms after starting treatment with ICIs. These symptoms must have appeared no more than 3 months after the last administration of ICIs.

Or

• Patients with an autoimmune disease of the central nervous system (diagnosis made by teams 1, 2 and 3) according to internationally recognised criteria, with no history of active cancer in the last 3 years and no other autoimmune disease Or
• Patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hypertension (diagnosed based on imaging (brain MRI) and clinical findings), with no history of active cancer in the last 3 years and no active autoimmune disease

Exclusion Criteria:

• Contraindication or refusal to perform a lumbar puncture
• Sample not suitable for research (volume of CSF collected for treatment >5 mL)
• Corticosteroid therapy or other immunomodulatory treatment in progress (discontinued less than 15 days prior to inclusion)
• Pregnant or breastfeeding women
• Not affiliated with the social security system, patients under French State Medical Aid for undocumented migrants
• Patients under guardianship or curatorship, under judicial protection measures, or deprived of their liberty by judicial or administrative decision

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group : cancer patients developing neurological symptoms after starting treatment with immune	Other: Lumbar puncture and blood sampling; For all patients in the study, lumbar puncture will be performed as part of their care, according to the clinical indication given by the referring physician. If the patient gives their consent, an additional volume of CSF will be collected for this study, so that the total volume collected (care plus research) does not exceed 5 mL. No lumbar puncture will be performed specifically for the study. Blood samples will also be collected: these are additional blood tubes collected during a blood sample taken as part of the treatment (as described in the section 'Minimal risks and constraints added by the research').
Experimental: Control group : cancer patients undergoing treatment with ICIs and experiencing neurological symptom	Other: Lumbar puncture and blood sampling; For all patients in the study, lumbar puncture will be performed as part of their care, according to the clinical indication given by the referring physician. If the patient gives their consent, an additional volume of CSF will be collected for this study, so that the total volume collected (care plus research) does not exceed 5 mL. No lumbar puncture will be performed specifically for the study. Blood samples will also be collected: these are additional blood tubes collected during a blood sample taken as part of the treatment (as described in the section 'Minimal risks and constraints added by the research').
Experimental: Control group : patients with an autoimmune disease of the central nervous system	Other: Lumbar puncture and blood sampling; For all patients in the study, lumbar puncture will be performed as part of their care, according to the clinical indication given by the referring physician. If the patient gives their consent, an additional volume of CSF will be collected for this study, so that the total volume collected (care plus research) does not exceed 5 mL. No lumbar puncture will be performed specifically for the study. Blood samples will also be collected: these are additional blood tubes collected during a blood sample taken as part of the treatment (as described in the section 'Minimal risks and constraints added by the research').
Experimental: Control group : patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hyperte	Other: Lumbar puncture and blood sampling; For all patients in the study, lumbar puncture will be performed as part of their care, according to the clinical indication given by the referring physician. If the patient gives their consent, an additional volume of CSF will be collected for this study, so that the total volume collected (care plus research) does not exceed 5 mL. No lumbar puncture will be performed specifically for the study. Blood samples will also be collected: these are additional blood tubes collected during a blood sample taken as part of the treatment (as described in the section 'Minimal risks and constraints added by the research').

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of nervous system-specific TCRs in CSF of patients with ICI-related neurotoxicity	Specific TCR repertoires of ICI-related neurotoxicity will be identified by TCR sequencing of CSF and blood lymphocytes of patients at the time of diagnosis of neurotoxicity of ICIs in comparison to those found in the control cohort 1.2. The target of these lymphocytes specifically found in cohort 1.1 will be assessed by EliSpot with known neuronal antigens as well as a search for serum and CSF onconeuronal autoantibodies. In silico methods as well as public TCR database will also be used to find the neurological targets.	At day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportions of lymphocytes	Absolute number and percentage of different cells subsets in CSF (CD3, CD20, CD4, CD8, C56) and of their phenotype (naif, effector memory, central memory, Treg) and expression profile will be assessed in study cohort and control cohorts by single cell RNA sequencing and flow cytometry.	At day 1
Concentration of pro and anti-inflammatory cytokines in CSF of patients with ICI-related neurotoxicity and control cohorts	Measurement of CSF cytokines concentration by Single-Molecule Array and comparison of their levels in the four cohorts. The comparaison of cohort 1.1 with control cohort 3 will allow us to determine the normal level of each cytokine, the comparaison with the other cohorts will lead to the identification of the specific cytokine profile of ICI-related neurotoixicity.	At day 1
Presence and strength of correlation between TCR repertoires and phenotype/ expression profile of CSF lymphocytes and clinical presentation of ICI-related neurotoxicity	Comparison of the proportions of TCR repertoire, phenotypic and expression profiles of the lymphocytes present in the CSF between the subgroups of patients with different neurological presentations (encephalitis, myelitis, meningitis, polyraduculonevritis, neuropathy) within the cohort 1.1 by using Spearman correlation.	At day 1

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): November 1, 2030

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Immune checkpoint inhibitors; Autoimmune neurological diseases; Neurotoxocities
• Additional Relevant MeSH Terms: Investigative Techniques; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Biopsy; Diagnostic Techniques, Neurological; Spinal Puncture; Blood Specimen Collection
• Other Study ID Numbers: APHP251304

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