TolDec-COMBINEM

Treatment tested

• AUTOLOGOUS TOLEROGENIC DENDRITIC CELLS

Inclusion: - Age between 18-65 years old. - Patients diagnosed with RRMS according to 2017 McDonald criteria (see Appendix 1). - 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). - One or more documented relapses within the 2 years before the screening with either: a) one relapse which occurred within the last year prior the screening of the study; b) the presence of ≥ 1Gd+ T1 lesion or ≥ 2 new T2 lesion within 12 months prior the screening of the study (i.e, compared with an cerebral MRI in the last 12 months). - 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: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogenonly hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence. Exclusion: - Presence of a relapse or use of steroids 30 days prior to screening visit. - 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. - 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.

To evaluate the radiological efficacy and safety of TolDec therapy in combination with first line immunotherapy in RRMS patients.