Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis

Our working hypothesis is to make a combination therapy with low-moderate efficacy immunomodulatory drugs with the aim of increasing efficacy without causing serious adverse effects such as those associated with the available high-efficacy therapies. Cellular therapies represent a highly specific treatment aimed to target selective "pathogenic" cells subsets. Tol-Dec loaded with immunogenic peptides interacts with Ag-specific T lymphocytes inducing regulatory T cells without affecting other cell subsets leading to a antinflammatory shift of immunological responses.

Inclusion criteria

• Age between 18-65 years old.
• Patients diagnosed with RRMS according to 2017 McDonald criteria.
• MS disease duration < 10 years.
• Expanded disability status scale (EDSS) from 0 to < 5.5.
• Patients eligible to start or already are in on treatment with first line immunomodulatory treatment (interferon beta 1a, interferon beta 1b, glatiramer acetate, teriflunomide or dymethyl-fumarate).
• Able to sign informed consent.
• Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence.

Exclusion criteria

• Presence of a relapse or use of steroids 30 days prior to screening visit.
• Concomitant use of any type of immunomodulatory / immunosuppressive therapy.
• Use of previous immunosuppressive or cytotoxic therapy in the last 6 months. Use of previous alemtuzumab, cladribine or bone marrow or stem cell transplant at any time.
• Patients unable or unwilling to undergo MRI scans.
• Severe systemic diseases or history of cancer or hereditary familiar cancer.
• Clinically relevant concomitant disease: cardiac, gastrointestinal, hepatic, pulmonary, neurological, renal or other major disease.
• Impossibility to proceed to the leukapheresis (e.g. absence of peripheral venous access).
• Pregnant or breastfeeding women.
• Drug or alcohol abuse.
• Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS or to test positive for HIV antibody at screening.
• Ongoing known bacterial, viral or fungal infection (with the exception of onychomycosis and dermatomycosis), positive hepatitis B surface antigen or hepatitis C antibody tests at screening.
• Patients with a known history of syphilis or tuberculosis or test positive for syphilis (positive rapid plasma reagin, RPR) or tuberculosis (positive skin test) at screening. Active or latent tuberculosis (TB).
• Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that may interfere with the compliance to the protocol.
• Any other clinically relevant medical or surgical condition, which, in the opinion of the investigator, would put the subject at risk by participating in the study.
• Participation in other experimental studies within the previous 90 days prior to screening visit.