Table 3.
A summary of the published results (2017–22) from mRNA cancer vaccine trials by type of formulation
| Trial phase | Target antigen | Cancer type | Patients, n | Combination | Immune response | Clinical response | |
|---|---|---|---|---|---|---|---|
| Non-formulated (naked) | |||||||
| NCT02035956 | 1 | An individualised tumour mutation signature with ten selected neoepitopes for each patient | Melanoma (stages III and IV) | 13 | None | T-cell responses against numerous vaccine neoepitopes | One (8%) patient had complete response and another patient (8%) had partial response10 |
| NCT03394937 | 1 | CD40L, CD70, caTLR4; tumour-associated antigens: tyrosinase, gp100, MAGE-A3, MAGE-C2, and PRAME | Resected melanoma (stages IIc, III, and IV) | 20 | None | Vaccine-induced immune responses in four (40%) of ten patients (low dose) and three (33%) of nine patients (high dose) | Not reported11 |
| Protamine formulation | |||||||
| NCT01817738 | 1/2 | PSA, PSMA, PSCA, STEAP1, PAP, and MUC1 | Metastatic castration-resistant prostate cancer | 197 | None | Not reported | No significant differences in progression-free survival12 |
| NCT00923312 | 1/2 | MAGE-C1, MAGE-C2, NY-ESO-1, survivin, and 5T4 | Non-small-cell lung cancer (stages IIIb and IV) | 46 | None | T-cell responses against at least one tumour-associated antigen in 19 (63%) patients | No objective responses; progression-free survival and overall survival not improved13 |
| NCT01915524 | 1 | MAGE-C1, MAGE-C2, NY-ESO-1, survivin, 5T4, and MUC-1 | Non-small-cell lung cancer (stage IV) | 26 | With local irradiation (with or without pemetrexed and with or without EGFR tyrosine-kinase inhibitor) | Detectable antigen-specific immunity in 21 (84%) patients | One (4%) patient had partial response in combination with chemotherapy treatment, and 12 (46%) patients had stable disease14 |
| Lipoplex formulation | |||||||
| NCT02410733 | 1 | NY-ESO-1, tyrosinase, MAGE-A3, and TPTE | Melanoma | 25 (monotherapy); 17 (combination) | With or without standard PD-1 therapy | Immune responses against a minimum of one tumour-associated 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 monotherapy: three (12%) patients had partial response, and seven (28%) had stable disease15 |
| NCT04503278 | 1/2 | CLDN6 (CARVac) | Solid tumours (CLDN6 CAR T cells with CARVac) | 7 | With CLDN6 CAR T cells | Engraftment of CAR T cells in all patients | Four (57%) patients had partial response and one (14%) patient had stable disease at the 6-week evaluation16, 17 |
| Lipid nanoparticle formulation | |||||||
| NCT03480152 | 1/2 | Neoantigen-specific mRNA | Gastrointestinal cancer | 4 | None | Mutation-specific CD4+ and CD8+ T-cell responses against predicted neoepitopes in three (75%) of four patients | No objective clinical responses18 |
| NCT03313778 | 1 | Personalised cancer vaccine encoding several neoantigens | Solid tumours (resected) | 13 (monotherapy); 19 (combination) | With pembrolizumab | Detectable neoantigen T-cell responses | Vaccine monotherapy: 12 patients were cancer-free on study treatment with a median follow-up of 8 months; combination treatment: one patient had complete response before vaccination, two patients had partial response, five patients had stable disease, five had disease progression, and two had unconfirmed disease progression19 |
CAR=chimeric antigen receptor.