Table 5 Clinical trials using T cell vaccination in MS patients
From: Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy
Vaccination type | Vaccine composition | NCT number | MS patients | Number of MS patients | Phase | Status | Study design | Dose and number of injections | Route of administration | Clinical outcome | TCV Center | Ref |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
T cell vaccination | Autologous MBP-reactive T cell clones (predominant reactivity pattern to MBP 84–102 and 143–168 peptides) | Unregistered | RRMS (n = 3) PPMS (n = 1) SPMS (n = 2) | 6 | Phase I | Completed | Non-randomized, open label | A total of 3 injections of 2–3 irradiated MBP-specific T cell clones (1 × 107 to 1.5 × 107 cells/clone) | s.c. | Decreased frequency of MBP-reactive T cells after the 2nd administration Remained undetectable in 5 of 6 patients at the end of the study | LUC, Diepenbeek, Belgium | |
T cell vaccination | Autologous MBP-reactive T cell clones | Unregistered | RRMS (n = 5) PPMS (n = 1) SPMS (n = 2) | 8 | Phase I | Completed | Non-randomized, open label | A total of 3 injections of 2–4 irradiated MBP-specific T cell clones (15 × 106 cells/clone) every 2–4 months | s.c. | Moderate clinical improvement by reduction of relapse rate, and brain lesions compared to paired controls | LUC, Diepenbeek, Belgium | |
T cell vaccination | Autologous MBP-reactive T cell clones both whole MBP and MBP peptides (83–99 and 151–170) | Unregistered | RRMS (n = 28) SPMS (n = 26) | 54 | Phase II | Completed | Non-randomized, open label | A total of 3 injections every 2 months of 2–4 irradiated MBP-T cell clones (30 × 106–60 × 106 cells/clone) | s.c. | Reduction of 40% in ARR MRI lesions and EDDS remained stable. | Baylor College of Medicine, Houston, TX, USA | |
T cell vaccination | Autologous specific T-cell lines against MBP((83–99, 87–110, 151–170) and/or MOG(G (6–26, 34–56) | NCT00220428 | RRMS with aggressive disease course and failure to respond to DMT | 20 | Phase I Phase II | Completed | Randomized, open label | A total of 3 injections in 6- to 8-week intervals of up to 1.5 × 107 cells of each myelin-reactive T cell line (not exceeding 6 × 107 total cells) | s.c. | Treatment was safe and no serious adverse events were observed. Decreased ARR, number and volume of active MRI lesions, as well as reduction in T2 lesion burden (quantitative MRI analysis) | Sheba Medical Center Ramat Gan, Israel | |
T cell vaccination | Autologous myelin-reactive T-cell lines against MBP, PLP, and MOG peptides | NCT00228228 | Patients with probable MS within up to 3 months after the first clinical attack | 80 | Phase I Phase II | Unknown | Randomized, double-blind | Dose: 1–1.5 × 107 cells/line, up to 5 lines Multiple injections: a total of 5 injections, 3 every 6 weeks and 2 boosts on weeks 24 and 28 | Unknown | To evaluate the treatment effects at the onset of disease, in patients with probable MS within up to 3 months after the first clinical attack, in order to evaluate whether early treatment can prevent the second attack (conversion to definite MS). | Sheba Medical Center Ramat Gan, Israel | |
T cell vaccination | Whole bovine myelin selected T cells | Unregistered | SPMS (n = 4) with EDSS > = 6.5 SPMS (n = 80) | Phase I, n = 4 Phase II, n = 80 | Phase I Phase II | Phase I completed | Non-randomized, open label | A total of 3 administrations every 3 months of 40 × 106 irradiated T cells | s.c. | TCV using autologous irradiated bovine myelin-reactive T cells depletes circulating MBP-specific T cells in patients | USC, Los Angeles, USA | |
CSF-derived T cell vaccination | CSF-derived T cell lines reactive to myelin peptides | Unregistered | PPMS (n = 4) | 4 | Phase I | Completed | Non-randomized, open label | Single, twice or 3 administrations of 4 × 106 irradiated CSF-derived T cell clones | s.c. | Administration of attenuated autoreactive CSF-derived T cell clones was feasible, and no adverse effects were observed | Harvard Medical School, Boston, USA | |
CSF-derived T cell vaccination | CD4+ T-cells derived from CSF | Unregistered | RRMS (n = 4) SPMS (n = 1) | 5 | Phase I | Completed | Non-randomized, open label | A total of 3 administrations every 2 months of 10 × 106 irradiated CSF-derived T cells vaccines | s.c. | Vaccinations were well tolerated; no adverse effects were found. Preliminary efficacy data exhibited clinical stability of patients and reduced EDSS with no relapses during or after treatment | LUC, Diepenbeek, Belgium | |
T cell vaccination | T cells lines reactive against 9 myelin peptides of MBP (84–102, 143–168), MOG (1–22, 34–56, 64–86, 74–96) and PLP (41–58, 184–199, 190–209) | NCT01448252 | Relapsing-progressive MS patients with EDSS from 3.0 to 7.0 | 26 MS patients: n = 19 patients treated with TCV and n = 7 patients treated with placebo | Phase I Phase II | Completed | Randomized double-blind, placebo-controlled | Dose: 10–30 × 106 irradiated autologous T-cells Multiple administrations: 4 vaccinations on days 1, 30, 90, and 180 | s.c. | Results demonstrate the feasibility and safety of the procedure and showed clinical improvements (decrease of EDSS and high frequency of relapse-free patients during the year of the study in TCV treated patients compared to placebo group) MRI parameters did not change significantly | Dept of Neurology, Hadassah Ein-Kerem Jerusalem, Israel | |
T cell vaccination Tcelna® (Imilecleucel-T, previously known as Tovaxin®) | Autologous T cells against 6 immunodominant peptides derived from MOG (MOG1–17, MOG19–39), PLP (PLP30–49, PLP180–199) and MBP (MBP83–99, MBP151–170) | NCT00587691 | RRMS (n = 9) SPMS (n = 7) | 16 | Phase I Phase II | Completed | Non-randomized, open label, dose-escalation study | Multiple administrations of 3 doses were tested. Low dose: 6–9 × 106, mid dose: 30–45 × 106 and high dose: 60–90 × 106 irradiated autologous myelin-reactive T cells, administrated on weeks 0, 4, 12, and 20 | s.c. | Tovaxin® was safe and well tolerated, and appeared to be associated with clinical benefit (reduction of ARR) The administration of 30–45 × 106 irradiated myelin-reactive T cells was the most effective dose during the 52 weeks study | Opexa Therapeutics, Inc. Texas, United States | |
T cell vaccination Tcelna® (Imilecleucel-T, previously known as Tovaxin®) | Autologous T cells against up to 6 immunodominant peptides derived from MBP, MOG, and PLP | NCT00245622 (TERMS study: Tovaxin for Early Relapsing Multiple Sclerosis) | RRMS (n = 95) CIS (n = 5) | 150 (Tovaxin, n = 100; placebo, n = 50) | Phase IIb | Completed | Randomized, double-blind, placebo-controlled. Personalized therapy as a result of prescreening reactivity against peptide libraries covering MBP, MOG and PLP | Multiple administrations: 5 injections of 30–45 × 106 irradiated autologous myelin-reactive T cells on weeks 0, 4, 8, 12, and 24 | s.c. | Tovaxin treatment had a safety profile but efficacy results were not clear likely due to the presence of patients with prior treatment with DMT therapies | Opexa Therapeutics, Inc. Texas, United States | |
T cell vaccination Tcelna® (Imilecleucel-T, previously known as Tovaxin®) | Autologous T cells against up to 6 immunodominant peptides derived from MBP, MOG, and PLP | NCT00595920 OLTERMS study: Open label extension of TERMS study | RRMS CIS with positive myelin-reactive T cells (MRTC) in their blood during the previous TERMS study | 116 | Phase II (extension study) | Terminated due to financial constraints | Multicenter, randomized, double-blind, placebo-controlled. Personalized therapy using prescreening reactivity test | Multiple administrations: 5 injections of 30–45 × 106 irradiated autologous myelin-reactive T cells on weeks 0, 4, 8, 12, and 24. yearly as required | s.c. | Since only 38 patients received the treatment and 32 of them did not complete the 5 administrations, it was not possible to evaluate the efficacy | Opexa Therapeutics, Inc. Texas, United States | – |
T cell vaccination Tcelna® (Imilecleucel-T, previously known as Tovaxin®) | Autologous pool of myelin-reactive T-cells against immunodominant epitopes selected derived from MBP, MOG and PLP on a per subject basis | NCT01684761 Abili-T study | SPMS Presence of myelin-reactive T-cells EDSS score 3.0–6.0, inclusively | 183 | Phase II | Completed | Multicenter, randomized, double-blind, placebo-controlled | Multiple administrations: 5 injections of 30–45 × 106 irradiated autologous myelin-reactive T cells on weeks 0, 4, 8, 12, and 24. | s.c. | Favorable safety and tolerability profile in SPMS patients No changes on disease progression rate nor reduction of brain atrophy was observed | Opexa Therapeutics, Inc. Texas, United States | – |
