Table 3.
Clinical trials of mRNA vaccines encoding TAAs
| Cancer type | NCT number | Drug administration | Phase | TAA type | Status | Delivery system | Result | |
|---|---|---|---|---|---|---|---|---|
| Respiratory system tumors (mainly non-small cell lung cancer) | non-small cell lung cancer | NCT03164772 | BI 1361849 (CV9202) + Durvalumab + / − Tremelimumab | I/II | EGFR | Recruiting | Protamine | Good tolerance, and most patients (84%) have found antigen specific immune responses [24] |
| NCT00923312 | mRNACV9201 | I/II | EGFR | Recruiting | Protamine | Good tolerance and immune response detected after treatment; The median progression and overall survival time were 5 months and 10.8 months, respectively [86] | ||
| NCT01915524 | With local irradiation (with or without pemetrexed and with or without EGFR tyrosine-kinase inhibitor) | I | EGFR | Recruiting | Naked RNA | Detectableantigen-specificimmunity in 21 (84%) patients. One (4%) patient had partial response in combination with chemotherapy treatment, and 12 (46%) patients had stable disease [25] | ||
| Reproductive system tumors | ovarian cancer | NCT04163094 | W_ova1 + carboplatin/paclitaxel | I | OVA-1 | Recruiting | Naked RNA | Not published |
| recurrent epithelialOC | NCT01334047 | DC-006 vaccine (mRNA encoding hTERT, survivin) | I/II | hTERT | Recruiting | DC | Not published | |
| Penile Neoplasms Malignant | NCT03418480 | BNT113 (HPV16 E6 and E7 oncoproteins) | I/II | E6/E7 | Recruiting | Unkown | Not published | |
| ovarian cancer | NCT01456065 | DCs loaded with TERT-mRNA and Survivin-peptide | I | TERT-mRNA and Survivin-peptide | Unknown | DC | Not published | |
| Skin tumor (mainly melanoma) | melanoma | NCT02410 733 | NY-ESO-1, tyrosinase, MAGE-A3, and TPTE | I | NY-ESO-1, MAGE-A3, tyrosinase, TPTE | Active, not publishedt recruiting | Lipid nanoparticles | Immune responses against a minimum of one tumourassociated antigen in 39 (75%) patients. mRNA vaccine with anti-PD-1 therapy: six (35%) patients had partial response and two (12%) had stable disease; mRNA vaccine monot publishedtherapy: three (12%) patients had partial response, and seven (28%) had stable disease [152] |
| NCT04526899 | BNT111 (NY-ESO-1, tyrosinase, MAGE-A3, and TPTE) + cemiplimab | II | NY-ESO-1, MAGE-A3, tyrosinase, TPTE | Recruiting | RNA-LPX | Good tolerance, strong CD4 + and CD8 + T cell immunity after treatment, combined with PD-1 inhibitors, achieving an objective response rate of 35% [153] | ||
| NCT00940004 | Dendritic cells electroporated with mRNA encoding gp100 and tyrosinase | I/II | gp100 | Completed | DC | Not published | ||
| NCT01676779 | mRNA; b.TAAs: MAGE-A3, MAGE-C2, tyrosinase, gp100 | II | NY-ESO-1, MAGE-A3, tyrosinase, TPTE | 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) [154] | ||
| NCT01302496 | mRNA; b.TAAs: MAGE-A3, MAGE-C2, tyrosinase, gp100 | II | NY-ESO-1, MAGE-A3. tyrosinase. TPTE | Completed | DC | 12 out of 15 patients showed T cell stimulation response.Some patients have strong immune responses; Both single therapy and combination therapy can induce multifunctional CD8 + T cell responses, which may provide a benchmark for achieving the immune stimulation levels required for sustained clinical remission [26] | ||
| NCT01676779 | mRNA; TAAs: MAGE-A3, MAGE-C2, tyrosinase, gp100 | II | mRNA; TAAs: MAGE-A3, MAGE-C2, tyrosinase, gp100 | 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) | ||
| NCT01456104 | Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs) | I | HLA-A | Completed | DC | Unknown | ||
| NCT00978913 | DCs transfected with hTERT, survivin and p53 | I | hTERT, survivin and p53 | Completed | DC | Unknown | ||
| NCT00961844 | Dendritic cells—transfected with hTERT-, survivin- and tumor cell derived mRNA + ex vivo T cell expansion and reinfusion + Temozolomid | I/II | hTERT-, survivin- and tumor cell derived mRNA | Terminated | DC | Unknown | ||
| NCT00929019 | Autologous dendritic cells electroporated with mRNA | I/II | HLA-A2 | Terminated | DC | Not reported | ||
| NCT01302496 | mRNA; b.TAAs: MAGE-A3, MAGE-C2, tyrosinase, gp100s | II | MAGE-A3, MAGE-C2, tyrosinase, gp100s | Completed | DC | Among the 15 patients, 12 had T cell stimulation response; Some patients have strong immune responses; Both single therapy and combination therapy can induce multifunctional CD8 + T cell responses, which may provide a benchmark for achieving immune stimulation levels required for sustained clinical remission [24] | ||
| Urinarysystem tumor (mainly prostate cancer) | Prostate cancer | NCT04382898 | BNT112 (PAP, PSA, and three undisclosed antigens) + cemiplimab | I/II | PAP, PSA, and three undisclosed antigens | recruiting | RNA-LPX | Not published |
| NCT01817738 | mRNA vaccine CV9104 | I/II | Terminated | Protamine | Not published | |||
| NCT01446731 | DCs transfected with PSA, PAP, survivin and hTERT mRNA + docetaxel | II | PSA, PAP, survivin and hTERT | Completed | DC | Not published | ||
| NCT02692976 | DC loaded with protamine/mRNA encoding keyhole limpet hemocyanin (KLH) + DC loading with MHC I binding peptides, NY-ESO-1 and MUC1 PepTivator® | II | keyhole limpet hemocyanin (KLH) | Completed | DC | Not published | ||
| NCT01197625 | Dendritic cell vaccine | I/II | PSA | Active, not recruiting | DC | Not published | ||
| NCT01153113 | Human telomerase reverse transcriptase mRNA (hTERT mRNA) transfected dendritic cell | I/II | hTERT | Withdrawn | DC | Not published | ||
| NCT00831467 | CV9103:PSA, PSCA, PSMA, STEAP1 | I/II | PSA, PSCA, PSMA, STEAP1 | Completed | Protamine | Good tolerance and immunogenicity | ||
| NCT00831467 | CV9103 (mRNA encoding 4 PSAs, PSCA, PSMA, and STEAP1) | I/II | PSAs, PSCA, PSMA, and STEAP1 | Completed | protamine-stabilized mRNA | well tolerated,prolonged patient survival | ||
| Blood System Cancer(leukemia mainly) | leukemia | NCT05000801 | Dendritic cell vaccine | I | PSAs, PSCA, PSMA, and STEAP1 | recruiting | DC | Not published |
| NCT01686334 | Dendritic cell vaccine | I/II | PSAs, PSCA, PSMA, and STEAP1 | recruiting | DC | Not published | ||
| NCT03083054 | Autologous dendritic cells electroporated with WT1 mRNA | I/II | WT1 | Not published | DC | Not published | ||
| NCT00834002 | Wilms Tumor Gene (WT1) mRNA-transfected autologous dendritic cell | I | WT1 | Completed | DC | Not published | ||
| NCT02649829 | dendritic cell vaccination plus chemotherapy | I/II | WT1 |
Active, not recruiting |
DC | Not published | ||
| NCT01734304 | DCs electroporated with mRNA encoding WT1, PRAME, and CMVpp65 | I/II | WT1, PRAME, and CMVpp65 | Completed | DC | Not published | ||
| NCT00510133 | GRNVAC1 (mRNA encoding human telomerase reverse transcriptase (hTERT) and a portion of the lysosome-associated membrane protein LAMP-1 (LAMP)) | II | hTERT, LAMP-1 (LAMP) | Completed | DC | Not published | ||
| NCT02528682 | MiHA mRNA-loaded PD-L-silenced DC | I/II | WT1 | Completed | DC | Not published | ||
| NCT01686334 | Autologous WT1 mRNA-electroporated DCs | II | WT1 | Recruiting | DC | Not published | ||
| NCT01995708 | CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells (LCs) | I | CT7, MAGE-A3, and WT1 | Active, recruiting | DC |
safe and therapeutic with a slight adverse event [24] |
||
| NCT03083054 | Autologous dendritic cells electroporated with WT1 mRNA | I/II | WT1 |
Active, not recruiting |
DC | Not published | ||
| NCT00965224 | mRNA encoding for Wilms’ tumor antigen WT1 | II | WT1 | Recruiting | DC | Not published | ||
| NCT00514189 | mRNA in AML cell lysate | I | WT1 | Recruiting | DC | Not published | ||
| NCT02405338 | mRNA encoding WT1 and PRAME | I/II | WT1 |
Active, not recruiting |
DC | Not published | ||
| Digestive System Cancer | Colorectal Cancer with Liver Metastases | NCT05533697 |
mRNA-4359 (mRNA encoding IDO and PD-L1) |
I/II | IDO | Recruiting | Unknown | ongoing |
| NCT00228189 | CEA mRNA-loaded DCs | I/II | CEA | Completed | DC | Not published | ||
| Neurological tumors | Glioblastoma | NCT03688178 | Cytomegalovirus pp65-LAMP + temozolomide, varlilumab, and Td | II | Recruiting | DC | Not published | |
| NCT00639639 | Cytomegalovirus pp65-LAMP + autologous lymphocyte transfer and Td | I | pp65-LAMP | Completed | DC | Not published | ||
| NCT04573140 | Autologous total tumor mRNA and pp65 full length (fl) lysosomal associated membrane protein (LAMP) mRNA loaded DOTAP liposome vaccine administered intravenously (RNA loaded lipid particles, RNA-LPs) | I | LAMP | Recruiting | RNA-LPX | Not published | ||
| NCT02649582 | Dendritic cell vaccine + temozolomide chemotherapy | I/II | WT1 | Recruiting | DC | No | ||
| NCT01291420 | WT1 mRNA-electroporated autologous dendritic cell | I/II | WT1 | Unknown | DC | No | ||
| NCT00961844 | mRNA encoding hTERT, survivin, and tumor mRNA | I/II | hTERT | Recruiting | DCs loaded and ex vivo T cell expansion and reinfusion | Not published | ||
| NCT02366728 | Human CMV pp65-LAMP mRNA-pulsed autologous DCs | II | pp65-flLAMP | Active, not recruiting | DC | Not published | ||
| NCT03548571 | Dendritic cell immunization + Adjuvant temozolomide | II/III | Active,not recruiting | DC | Not reported | |||
| Other Cancers | unresectable/metastatic/recurrent head and neck cancer | NCT04534205 | BNT113 (mRNA encoding E6/E7) | II | E6/E7 | Active, not recruiting | LPX | Not published |