Table 3.
Selected therapeutic mRNA-based vaccines for glioblastomas in clinical trials
| NCT number | Study title | Study status | Conditions | Interventions | Results | Current responsible party | Study phase | Enrollment |
|---|---|---|---|---|---|---|---|---|
| NCT00846456 | Safe study of DC-based therapy targeting CSCs in GBM | Completed |
GBM Brain tumor |
BIOLOGICAL: DC vaccine with mRNA from CSCs | Progression-free survival: 694 days (vaccinated) vs. 236 days (controls, p = 0.0018). OS trend: 759 days (vaccinated) vs. 585 days (controls, p = 0.11). Specific T-lymphocyte proliferation in response to tumorsphere lysate, hTERT, or survivin peptides. MRI findings showed initial increase in contrast-enhancing lesions followed by a significant reduction | Steinar Aamdal, Oslo University Hospital | 1 and 2 | 20 |
| NCT02529072 | Nivolumab with DC vaccines for recurrent brain tumors | Completed |
Malignant GBM Astrocytoma GBM |
DRUG: nivolumab BIOLOGICAL: DC Group I: nivolumab 3 mg/kg IV every 2 weeks for 8 weeks Group II: nivolumab 3 mg/kg IV + DC vaccine every 2 weeks for 3 doses, then surgery, followed by nivolumab every 2 weeks and DC vaccine monthly for 5 more doses |
Group II showed a longer median OS (15.3 months) compared to Group I (8.0 months) Progression-free survival was also longer in Group II (6.3 months) compared to Group I (4.3 months) Serious adverse events were more common in Group II (66.67%) compared to Group I (33.33%) |
Gary Archer, Duke University | 1 | 6 |
| NCT02808364 | Personalized cellular vaccine for recurrent GBM (PERCELLVAC2) | Completed | GBM | Personalized cellular vaccine consisting of mRNA tumor antigen pulsed autologous DCs administered biweekly | Antigen-specific CD4+ and CD8+ T cell responses were induced without obvious autoimmune adverse events | Jian Zhang, Guangdong 999 Brain Hospital | 1 | 10 |
| NCT00626483 | Basiliximab in treating patients with newly diagnosed GBM undergoing targeted immunotherapy and TMZ-caused lymphopenia | Completed | Malignant neoplasms brain |
Basiliximab [20 mg or 40 mg (two doses per cycle)] Temozolomide (TMZ) [75 mg/m2 (during RT), 150–200 mg/m2 (post-RT)] RNA-loaded DC vaccine (2 × 107 cells per dose, administered monthly) GM-CSF (administered intradermally with each vaccine) Radiotherapy (RT) (stereotactic, concurrent with initial TMZ course) |
Not reported | Gary Archer, Duke University | 1 | 34 |
| NCT02366728 | DC migration study for newly diagnosed GBM | Completed |
GBM Astrocytoma, grade IV Giant cell GBM GBM |
Group I: 1 × 106 unpulsed DCs (0.4 mL) one side of groin + 2 × 107 CMV pp65-LAMP DCs (up to 10 vaccines) + 111In-labeled DCs (4th vaccine) + temozolomide (150–200 mg/m2/d) + Saline (0.4 mL) opposite groin Group II: Td toxoid (1 flocculation unit, 0.4 mL) one side of groin + 2 × 107 CMV pp65-LAMP DCs (up to 10 vaccines) + 111 In-labeled DCs (4th vaccine) + temozolomide (150–200 mg/m2/d) + Saline (0.4 mL) opposite groin Group III: basiliximab (20 mg I.V. pre-vaccines) + Td toxoid (1 flocculation unit, 0.4 mL) one side of groin + 2 × 107 CMV pp65-LAMP DCs (up to 10 vaccines) + temozolomide (150–200 mg/m2/d) + saline (0.4 mL) opposite groin |
Group I: 25 participants, 23 completed, 4 not completed; Median OS: 16 months; median progression-free survival: 6.5 months; % of 111 In-labeled DCs migrating to inguinal lymph nodes: 6.0% Group II: 27 participants, 27 completed, 1 not completed; median OS: 20 months; median progression-free survival: 6.7 months; % of 111In-labeled DCs migrating to inguinal lymph nodes: 9% Group III: 8 participants, 8 completed, 1 not completed; median OS: 19 months; median progression-free survival: 7.1 months; % of 111In-labeled DCs migrating to inguinal lymph nodes: not collected |
Mustafa Khasraw, Duke University | 2 | 64 |
| NCT00890032 | Vaccine therapy in treating patients undergoing surgery for recurrent GBM | Completed | Recurrent CNS neoplasm |
BIOLOGICAL: BTSC mRNA-loaded DCs Initial dose: 2 × 106 BTSC mRNA-loaded DCs Escalation: 5 × 106, 2 × 107 per vaccination |
Not reported | John Sampson, Duke University | 1 | 50 |
| NCT00639639 | Vaccine therapy in treating patients with newly diagnosed GBM | Completed | Malignant neoplasms of brain |
BIOLOGICAL: tetanus toxoid BIOLOGICAL: therapeutic autologous DCs BIOLOGICAL: therapeutic autologous lymphocytes |
Not reported | Gary Archer, Duke University | 1 | 42 |
| NCT04741984 | Monocyte antigen carrier cells for newly diagnosed GBM | Withdrawn | GBM | BIOLOGICAL: MT-201-GBM monocyte vaccine [monocytes isolated from patient’s leukapheresis loaded with CMV pp65-LAMP (lysosomal-associated membrane protein) mRNA (messenger ribonucleic acid)] | Not reported | Michael Gunn, Duke University | 1 | – |
| NCT03927222 | Immunotherapy targeted against CMV in patients with newly diagnosed WHO grade IV unmethylated GBM | Terminated | GBM |
BIOLOGICAL: human CMV pp65-LAMP mRNA-pulsed autologous DCs containing GM CSF (2 × 107 cells, intradermally, bilaterally at groin site) DRUG: temozolomide (100 mg/m2/day for 21 days post-RT) BIOLOGICAL: tetanus–diphtheria toxoid (Td) (0.5 mL intramuscularly, 0.4 mL intradermally) BIOLOGICAL: GM-CSF (250 mcg, reconstituted in 0.5 mL of sterile water) BIOLOGICAL: 111-indium-labeling of cells for in vivo trafficking studies (50 μCi/5 × 107 DCs labeled) |
Not reported | Mustafa Khasraw, Duke University | 2 | 6 |
| NCT04911621 | Adjuvant DC immunotherapy for pediatric patients with high-grade GBM or diffuse intrinsic pontine GBM | Active_not_Recruiting |
High-grade GBM diffuse intrinsic pontine GBM |
BIOLOGICAL: DC vaccination + TMZ-based chemoradiation BIOLOGICAL: DC vaccination + conventional next-line treatment |
Not reported | University Hospital, Antwerp | 1 and 2 | 10 |
| NCT02465268 | Vaccine therapy for the treatment of newly diagnosed GBM | Active_not_Recruiting |
GBM|GBM Malignant GBM Astrocytoma, grade IV GBM |
Experimental: pp65-shLAMP DC with GM-CSF and Td Experimental: pp65-flLAMP DC with GM-CSF and Td Placebo comparator: unpulsed PBMC and saline |
Not reported | University of Florida | 2 | 175 |
| NCT03688178 | DC migration study to evaluate TReg depletion In GBM patients with and without Varlilumab | Active_not_Recruiting | GBM |
Group 1: DC vaccine (unpulsed DC pre-conditioning), temozolomide, up to 10 DC vaccines Group 2: DC vaccine (Td pre-conditioning), temozolomide, up to 10 DC vaccines Group 3: DC vaccine + varlilumab (Td pre-conditioning), temozolomide, up to 10 DC vaccines, and varlilumab infusions |
Not reported | Annick Desjardins, Duke University | 2 | 43 |
| NCT04573140 | A study of RNA-lipid particle (RNA-LP) vaccines for newly diagnosed pediatric high-grade GBMs (pHGG) and adult GBM | Recruiting | Adult GBM | BIOLOGICAL: autologous total tumor mRNA and pp65 full length lysosomal associated membrane protein mRNA loaded DOTAP liposome vaccine administered intravenously (RNA loaded lipid particles, RNA-LPs) | Not reported | University of Florida | 1 | 28 |
| NCT05938387 | Safety and tolerability of CVGBM in adults with newly diagnosed MGMT-unmethylated GBM or astrocytoma | Recruiting | GBM |
Dose escalation (part A): – Dose level -1: CVGBM 6 μg – Dose level 1: CVGBM 12 μg – Dose level 2: CVGBM 25 μg – Dose level 3: CVGBM 50 μg – Dose level 4: CVGBM 100 μg Dose expansion (part B): – CVGBM 100 μg (RDEa) |
Not reported | CureVac | 1 | 54 |
| NCT03396575 | Brain stem GBMs treated with adoptive cellular therapy during focal radiotherapy recovery alone or with dose-intensified TMZ | Recruiting |
Diffuse intrinsic pontine GBM (DIPG) Brain stem GBM |
BIOLOGICAL: TTRNA-DC vaccines with GM-CSF BIOLOGICAL: TTRNA-xALT DRUG: cyclophosphamide + fludarabine lymphodepletive conditioning|DRUG: dose-intensified TMZ DRUG: Td vaccine BIOLOGICAL: autologous HSC |
Not reported | University of Florida | 1 | 21 |
| NCT02649582 | Adjuvant DC-immunotherapy plus TMZ in GBM patients | Recruiting | GBM | BIOLOGICAL: DC vaccine plus TMZ chemotherapy (150–200 mg/m2/d temozolomide) | Not reported | Zwi Berneman, University Hospital, Antwerp | 1 and 2 | 20 |
GBM: glioblastoma; DCs: dendritic cells; WHO: World Health Organization; GM-CSF: granulocyte-macrophage colony-stimulating factor; CMV: cytomegalovirus; TReg: regulatory T cells; PD-L1: programmed death-ligand 1; LPs: lipid nanoparticles; CSCs: cancer stem cells; BTSCs: brain tumor stem cells; Td: tetanus–diphtheria toxoid; DIPG: diffuse intrinsic pontine GBM; TMZ: temozolomide; HSCs: hematopoietic stem cells