Table 5.

Clinical trials using T cell vaccination in MS patients

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	160
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	161
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	166
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	169
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	165
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	162
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	168
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	167
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	163
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	164
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	170
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	–

ARR annualized relapse rate, DMT disease-modifying treatments, i.d. intradermal IFA, incomplete Freund’s adjuvant, MBP myelin basic protein, MS multiple sclerosis, MOG myelin oligodendrocyte glycoprotein, PLP proteolipid protein, PPMS primary-progressive MS, RRMS relapsing-remitting MS, s.c. subcutaneous, SPMS secondary-progressive MS, TCV T cell vaccination, WBC white blood cell counts