Trial to Assess the Safety and Feasibility of Adoptive Cell Therapy With Autologous EBV-specific Cytotoxic T Lymphocytes (CTL) in Patients With a First Clinical Episode Highly Suggestive of Multiple Sclerosis (MS and EBV-CTL)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Know the risks and potential benefits of clinical studies and talk to your health care provider before participating.
Read our disclaimer for details.
The etiologic mechanisms involved in multiple sclerosis (MS) are not yet fully understood. Indeed MS is a multifactorial disease involving genetic and environmental factors and Epstein-Barr-Virus (EBV) could be one of these factors. However the link between EBV infection and the immunological mechanisms underlying MS is not clear. Robust sero-epidemiological evidences support an association between EBV infection and MS, and immunological data suggest an altered/deficient immune response against this virus. In healthy individuals EBV produces a persistent infection that is tightly controlled by the immune system. In patients with MS, cellular and humoral immune studies demonstrate an altered response against the virus with a T-cell abnormal reactivity against the EBV-infected autologous B-cells, elevated humoral immune response to Epstein Barr Nuclear Antigen-1, and in the case of children, an increased EBV shedding, demonstrating frequent EBV reactivations. Thus, it has been proposed, that patients with MS present a partially inefficient control of the EBV infection. Some experimental data support the hypothesis suggesting that the presence of autoreactive EBV-B cells in the meninges of patients, probably due to an insufficient clearance of these cells by the immune system, lead to the infiltration of autoreactive T cells. Another hypothesis also suggests a deficient control of the virus, in that case during the inactive phase of the disease. Together, the above data and hypotheses lead to the notion that an immune intervention capable of restoring the host-EBV balance could be beneficial to MS patients In this project, we will assess the feasibility and safety of autologous transfer of several amounts of CD8 T cells directed against autologous EBV transformed B cell lines, in order to finally restore an efficient control of EBV in MS patients. The main objective of the project is to test the feasibility and safety of the process, while efficacy parameters will be also assessed in secondary objectives.
Condition or disease
Other: Cellular therapy with EBV specific autologous CTL infusion
An Open Single-center, Phase I Proof of Concept Trial to Assess the Safety and Feasibility of Adoptive Cell Therapy With Autologous EBV-specific Cytotoxic T Lymphocytes (CTL) in Patients With a First Clinical Episode Highly Suggestive of Multiple Sclerosis
Study Start Date :
Estimated Primary Completion Date :
Estimated Study Completion Date :
Resource links provided by the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study:
18 Years to 45 Years (Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Patients with :
A clinically isolated syndrome (first acute or sub acute neurological event consistent with demyelination [i.e. optic neuritis, spinal cord syndrome, brainstem/ cerebellar syndrome])
And a MRI scan showing dissemination of MRI lesions in space based on Swanton criteria At least 1 lesion detected in 2 or more following locations (sites) periventricular, juxtacortical, infratentorial, spinal cord
With a possible dissemination of MRI lesions in time based on the revised McDonald criteria1 i.e. at least simultaneous detection of one Gadolinium (Gd) enhancing asymptomatic lesion with at least one no Gd enhancing lesion
EDSS Score <3
Patients covered by health care insurance (social security)
Written informed consent obtained.
Onset of symptoms occurring within 60 days of inclusion
Patients with HIV, HTLV, Hepatitis B, C Syphilis testing negative within 30 days
Positive EBV serology
White blood cell count (Leukocytes) > 750/mm3
Negative pregnancy test
Patients with clinically definite multiple sclerosis
Patients known to have HIV, HTLV Hepatitis A, B, C or Syphilis infections or patient with active uncontrolled systemic bacterial, viral, or fungal infections.
Patients with white blood cell count (Leukocytes) < 750/mm3
Pregnant or breast feeding women
No effective contraceptive method
Patients wishing to be pregnant during the course of the study
Patients under legal guardianship
Concomitant participation of any other trial
Patients with mental or psychiatry condition unable to understand the trial
Patients with any medically unstable condition or any health conditions that may impact the safety of the patient as determined by the investigator or patient with any stable condition treated with immunotherapy
Patients with a history of cancer within 5 years or progressive cancer except for basal or cell skin lesions surgically excised and cured, in situ cervical cancer
Patients unable to comply with protocol.
Contraindication for MRI or/and any known history of hypersensitivity to contrast medium
Patients currently treated with immunosuppressive drugs including oral or systemic corticosteroids