Table 2.
Clinical trials of mRNA vaccine against single tumor
| Registration number |
Status | Diseases | Phase | Encoding mRNA | Adjuvants | Delivery Tools | Additional therapies | Outcomes | ref |
|---|---|---|---|---|---|---|---|---|---|
|
Registration number |
Status | Diseases | Phase | Encoding mRNA | Adjuvants | Delivery Tools | Additional therapies | Outcomes | ref |
| NCT03394937 | Terminated | Melanoma | I | TAA: gp100, tyrosinase, MAGE-A3, MAGE-C2, PRAME | TriMix |
Synthetic naked mRNA |
- | Immunologically active cells against cancer were activated and expected potential risks are non-serious and related to the local administration of the product | [53] |
| NCT01066390 | Completed | Melanoma | IB | TAA: either gp100, MAGE-A3, MAGE-C2 or tyrosinase | TriMix | DCs-based | - | 15 patients tolerated administration of the vaccine well. Four durable objective tumor responses were observed during a follow-up over 2 years. Antigen-specific skin infiltrating lymphocytes were detected in 6/12 patients | [154] |
| NCT01676779 | Completed | Melanoma | II | No exact details | TriMix | DCs-based | - | 71% of patients in TriMix cohort were alive and free of disease compared to 35% in the control cohort after 1 year into the group. 9/21 patients in TriMix cohort experienced a non-salvageable melanoma recurrence compared to 14/20 in the control cohort after a median follow-up of 53 months | [181] |
| NCT01302496 | Completed |
Melanoma Stage III/ IV |
II | TAA: tyrosinase, gp100, MAGE-A3, or MAGE-C2 | TriMix | DCs-based | Ipilimumab | T-cell responses against antigens were detected in 12/15 patients. Treated patients resulted in an OS of 28% and a PFS of 18% during follow-up over 5 years | [155] |
| NCT02410733 | Active, not recruiting | advanced melanoma | I |
TAA: NY-ESO-1, Tyrosinase, MAGE-A3, TPTE |
- | Cationic liposomes | anti-PD1 therapy | Exploratory interim analysis showed that long-lasting antigen-specific CD4/8 + T cell responses were induced and regression of lesions was observed in multiple patients within 300 days of initiation of treatment | [156] |
| NCT02035956 | Completed |
Melanoma Stage III/ IV |
I |
TSA: poly-neoepitope; RBL001/RBL002 |
- | Naked mRNA | - | T cell response were detected in 60% selected neoepitopes. 75% of the patients had a progression-free survival of 27 months | [159] |
| NCT01684241 | Terminated | Metastatic melanoma | I |
TAA: MART, tyrosinase, gp100, MAGE-3 |
- | DCs-based |
GITR-L, Anti-CTLA4 mAb |
Antigen-specific immune responses against TAAs and survival were enhanced when vaccines combing with GITR-L and anti-CTLA-4 mAb | [153] |
| NCT00978913 | Completed | Melanoma | I |
TAA: hTERT, survivin, p53 |
- | DCs-based | Cyclophosphamide | Immune responses were detected in 6/17 patients by IFNγ ELISpot and 4/17 patients by proliferation assay. 9/22 treated patients achieved disease stabilization, 3/18 evaluable patients experienced tumor shrinkage | [182] |
| NCT00243529 | Completed |
Melanoma Stage III/ IV |
I/II |
TAA: Tyrosinase, gp100 |
- | DCs-based | - | TAA-specific CD4/CD8 + T cell responses were detected in 17/26 stage III patients and 11/19 stage IV patients. Stage IV patients with TAA-specific CD8 + T cell responses had a median overall survival of about 12 months longer than those who without response | [183] |
| NCT02285413 | Completed |
Melanoma Stage III/ IV |
II |
TAA: Tyrosinase, gp100 |
- | DCs-based | Cisplatinum | 44% antigen-specific CD8 + T cells and 28% functional T cell responses were detected in skin infiltrating lymphocytes from vaccinated patients with cisplatin. The relevant data were 67% and 19% for those vaccinated alone | [157] |
| NCT00204607 | Completed |
Melanoma Stage III/ IV |
I/II |
TAA: gp100, Melan-A, MageA3, survivin, MageA1, tyrosinase |
GM-CSF | Protamine | - | Vaccine-induced T cells were increased in 2/4 immunologically evaluable patients and a complete response was observed in 1/7 patients with measurable disease | [184] |
| NCT00678119 | Completed | Renal cell carcinoma | II | TAA and immune modulators | CD40L | DCs-based | sunitinib | 62% patients experienced clinical benefit (9 partial responses, 4 with stable disease), and five patients (24%) survived for more than 5 years | [185] |
| NCT01890213 | Completed | Colorectal Cancer | I | TAA: CEA | - | VRP | - | CEA-specific humoral immunity was observed in all involved patients. For patients with stage IV cancer, 5-year survival was 17%, (95% CI 6% to 33%). For patients with stage III cancer (n = 12), the 5-year RFS was 75%, (95%CI 40% to 91%) | [186] |
| NCT00228189 | Completed | Colorectal Cancer | I/II | TAA: CEA | - | DCs-based | - | The median PFS after mRNA-loaded DCs treatment was 26 months and median PFS for patients with peptide-loaded DCs treatment was 18 months | [187] |
| Completed | GBM | I |
TAA: containing 3–13 different TAAs |
- | DC-based | low-dose cyclophosphamide, imiquimod poly I:C, and anti-PD-1 antibody | TAA-specifc CD4 + or CD8 + T cell responses were detected in 2/5 GBM patients. The median survival time was 19 months for the GBM patients | [188] | |
| NCT00846456 | Completed | GBM | I/II | GSCs mRNA | - | DC-based | - | For vaccinated patients, the PFS was 694 days; for control group, the PFS was 236 days | [189] |
| NCT01686334 | Recruiting | AML | II | TAA: WT1 | - | DC-based | low-intensity chemotherapy | 5/10 patients with high WT-1expression showed molecular remission after vaccination, of 2 patients achieved complete remission | [190] |
| NCT01278940 | Completed | Melanoma | I/II | No exact details | - | DCs-based | IL-2 | Higher T cell proliferation to transferred DCs (tDC) than mockDC controls were observed in 10/19 patients. tDC-specific response was still detected over 10 weeks after last vaccination in 4/6 patients | [191] |
| NCT03164772 | Completed | NSCLC | I/II | TAA: MAGE-C1、NY-ESO-1、MAGE-C2、survivin、5T4, MUC-1 | - | Protamine | Durvalumab, Tremelimumab | Vaccine was well-tolerated, and immune responses against TAAs were detected in majority of patients | [53] |
| NCT00923312 | Completed | NSCLC | I/II | TAA: NY-ESO-1, 5T4, MAGE-C1, MAGE-C2, survivin, MUC-1 | - | LNP | - | CV9201 was well-tolerated. Median PFS and OS were 5.0 months (95% CI 1.8–6.3) and 10.8 months (8.1–16.7) since first administration. 2- and 3-year survival rates were 26.7% and 20.7%, respectively | [192] |
| NCT01915524 | Terminated | NSCLC | I | TAA: NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, MUC-1 | - | Protamine | Pemetrexed | 80% patients had elevated levels of antigen-specific antibodies and 40% had elevated levels of functional T cells. 46.2% patients achieved stable disease | [193] |
| NCT01446731 | Completed | Prostate cancer | II | TAA: PSA, PAP, survivin, hTERT | - | DCs-based | Docetaxel | PFS and OS were 5.5 and 21.9 months, respectively, for patients receiving docetaxel monotherapy and 5.7 and 25.1 months, respectively, for patients receiving combination therapy | [158] |
| EudraCT number:2008–003,967-37 | Completed | Prostate cancer | I/II | TAA: PSA, PSCA, PSMA, STEAP1 | - | protamine | - | A cellular immune response was observed in 25/33 of the patients. median OS was 31.4 months [95% CI: 21.2] for 36 treated patients with metastatic prostate cancer | [194] |
NSCLC non-small cell lung cancer, GBM glioblastoma, GSMs Glioma stem cells, AML acute myeloid leukemia, TAA tumor-associated antigen, TSA tumor specific antigen, LNP Liposome nanoparticles