Table 6.
Clinical trials of mRNA vaccines encoding immunomodulator
| Cancer type | NCT number | Drug administration | Phase | Immunomodulator | Status | Delivery system | Result | |
|---|---|---|---|---|---|---|---|---|
| Respiratory system tumors (mainly non-small cell lung cancer) | non-small cell lung cancer | NCT02688686 | Suppressor of cytokine signaling (SOCS) 1, MUC1 and Survivin mRNA-loaded DC + cytokine-induced killer | I/II | suppressor of cytokine signaling (SOCS) 1 | Unknown | DC | No |
| Skin tumors | Melanoma | NCT01066390 | TriMix-DC | I | TLR4, CD40L and CD70 | Completed | DC | 15 patients had good tolerance, 2 patients had complete remission, and 2 patients had partial remission; It has immunogenicity and long-lasting anti-tumor activity for disease control. Antigen specific CD8 + T cells were detected in 4 out of 5 patients [24] |
| NCT00204607 | mRNA + GM-CSF | I/II | GM-CSF | Completed | Naked RNA | Not reported | ||
| NCT00204516 | mRNA coding for melanoma associated antigens + GM-CSF | I/II | GM-CSF | Completed | Naked mRNA | Not published | ||
| NCT01278940 | mRNA-transfected DCs + IL-2 | I/II | IL-2 | Completed | DC | Not reported | ||
| NCT01530698 | autologous dendritic cell vaccine by mRNA Electroporation | I/II | TLR7/8, IL-6 | Completed | DC | Not reported | ||
| NCT04335890 | Vaccination with IKKb matured Dendritic Cells | I | IL-1ß, IL-6 and PGE2 | Active,not recruiting | DC | Not reported | ||
| NCT03394937 | CD40L, CD70, TLR4; tumour-associated antigens: tyrosinase, gp100, MAGE-A3, MAGE-C2, and PRAME | I | CD40L, CD70, TLR4; | Terminated | DC | Good tolerance, low dose (600 μ g) 4/10 and 3/9 of patients with high (1800ug) levels detected vaccine induced immune responses, with immunogenicity in some patients; No adverse reactions of level 3 or above have occurred [32] | ||
| NCT01676779 | mRNA; b.TAAs: MAGE-A3, MAGE-C2, tyrosinase, gp100 | II | Completed | DC | Good tolerance (symptoms: transient local skin reactions, flu like symptoms, shivering after infusion), and may increase the one-year survival rate (71% in the treatment group, 35% in the control group) | |||
| NCT03291002 | CV8102: TLR7/8, RIG-1 | I | TLR7/8, RIG-1 | Active,not recruiting | Protamine | Both individual and combined administration showed good therapeutic effects, and local induced immune responses were observed to transform into systemic immune responses | ||
| Solid Tumor | NCT03946800 | MEDI1191 (mRNA encoding IL-12) | I | IL-12 | Recruiting | LNP | Preliminary results from the initial clinical trial revealed that sequential or combination therapy of MED I1191 with durvalumab in patients with advanced solid tumors and skin or subcutaneous lesions is safe and feasible. No treatment-related adverse events leading to treatment discontinuation from MEDI1191 or durvalumab were reported. The combination of MEDI1191 and durvalumab has demonstrated preliminary clinical efficacy; 29.0% of patients achieve either a partial response (PR) or stable disease (SD) for a minimum duration of 12 weeks [179] | |
| NCT04455620 |
BNT151 (mRNA encoding IL-2) |
I/II | IL-2 | Recruiting | LPX | Ongoing | ||
| NCT04710043 |
BNT152 (mRNA encoding IL-7) plus BNT153 (mRNA encoding IL-2) |
I | IL-7/IL-2 | Recruiting | LPX | Ongoing | ||
| NCT05392699 | ABOD2011 (mRNA encoding IL-12) | I | IL-12 | Recruiting | Naked-mRNA | Ongoing | ||
| Neurological tumors(mainly glioblastoma) | glioblastoma | NCT03396575 | TTRNA-DC vaccines with GM-CSF | I | GM-CSF | Recruiting | DC | No |
| NCT02465268 | HCMV pp65-shLAMP or pp65-flLAMP + temozolomide, GM-CSF, and Td | II | GM-CSF | Recruiting | DC | Not published | ||
| NCT04963413 | Autologous DCs derived from PBMC loaded with RNA encoding the human CMV matrix protein pp65-LAMP plus GM-CSF | I | GM-CSF | Active,not recruiting | DC | Not published | ||
| NCT00626483 | CMV pp65-LAMP mRNA-loaded DC + GM-CSF | I | CMV pp65-LAMP | Completed | DC | Not published | ||
| NCT03927222 | Human CMV pp65-LAMP mRNA-pulsed autologous DCs + temozolomide + tetanusdiphtheria toxoid + GM-CSF | II | CMV pp65-LAMP | Recruiting | DC | Not published | ||
| Urinarysystem tumor (mainly prostatecancer) | Prostate cancer | NCT02452307 | Peptide vaccine + montanide ISA-51 + / − GM-CSF + / − imiquimod + / − mRNA/protamin | I/II | GM-CSF | Unknown | Protamine | No |
| Blood System Cancer(leukemia mainly) | leukemia | NCT00514189 | Autologous dendritic cells | I | GM-CSF | Terminated | DC | No |
| NCT02693236 | Adenovirus-transfected autologous DCs + CIK cells | I/II | cytokine-induced killer (CIK) cell | Unknown | DC | No | ||
| Digestive System Cancer | Colorectal Cancer with Liver Metastases | NCT04157127 | Pancreatic adenocarcinoma mRNA and lysate With standard therapy | I | Th-1 | Recruiting | DC | No |
| NCT03323398 | mRNA-2416:OX40L | I/II | OX40L | Active, not recruiting | Lipid nanoparticles | Good safety and tolerability, with no occurrence of > Level 3 adverse reactions; 14/39 patients were in stable condition, and 4/6 patients with ovarian cancer were in stable condition. The patients receiving treatment showed that OX40L protein and T cell infiltration in the tumor microenvironment increased, PD-L1 transcription was up-regulated, and the expression of proinflammatory genes was activated [154]. | ||
|
Colon Cancer Gastrointestinal Cancer |
NCT03739931 | mRNA-2752:OX40L, IL-23, IL-36Y | I | OX40L, IL-23, IL-36Y | Recruiting | Lipid nanoparticles | Good tolerance; Tumor shrinkage is related to drug use. 0.5 mg RNA combined with Duvalimab, 81% of bladder cancer focus regression was observed; Treatment has a sustained immune regulatory effect, with elevated levels of IFN-y, TNF-a, and PD-L1 detected in tumors and plasma [178]. | |
| Other Cancer | Ductal carcinoma in situ | NCT02872025 |
mRNA-2752 (mRNA encoding OX40L, IL-23, and IL-36γ) |
I | OX40L, IL-23, and IL-36γ | Recruiting | LNP | well tolerated with slight dose-limiting toxicities |