From: Clinical and immunological effects of mRNA vaccines in malignant diseases
Mrna encoding for | Vehicle | Entity | Outcome | Reference |
---|---|---|---|---|
WT1 | DC | AML | Induction/maintenance of CR. Clinical responses correlated with vaccine-associated increases in WT1-specific CD8+ T cells | NCT00834002 [156] |
WT1 | DC | Solid tumors | Unknown; in malignant pleural mesothelioma undefined clinical benefit, vaccine-elicited immunity was obtained in 9/10 pat. | NCT01291420 [157] |
WT1 | DC | AML | Prevent or delay relapse in 43% of patients with AML in remission after chemotherapy | NCT00965224 [158] |
WT1/PRAME | DC | AML | Specific T cell responses in 4/5 patients; CR after 21,25,33 months in 3 pat. | [159] |
WT1/PRAME/cmvpp65 | DC | AML | 2/7 pat. Exhibited responses to PRAME and WT each. 7/10 vaccinated pat. are still alive, and 5/10 are in CR, with an observation period of up to 840 d | NCT01734304 [160] |
hTERT | DC | AML | Maintenance of CR: 11 pat. (58%) developed hTERT-specific T-cell responses; median follow-up of 52 months, 58% of pat. In CR (11 of 19 patients) were free of disease recurrence | NCT00510133 [161] |
Whole tumor RNA | DC | Pediatric brain cancer | 2 of 7 pat. SD clinical and 1 of 7 showed a PR | [15] |
Tumor RNA plus synthetic CD40L RNA | DC | Metastatic RCC | In combination with sunitinib: 13 pat. (62%) experienced clinical benefit (9 PR, 4 SD); | NCT00678119 [162] |
NY-ESO-1, MAGE-A3, tyrosinase and TPTE | RNA-lipoplexes (iv) | Melanoma | Ifnα and strong antigen-specific T-cell responses were induced, SD/PR | [124] |
MAGE-C1, MAGE-C2, NY-ESO-1, BIRC5, 5T4 | Vaccine containing self-adjuvanted mRNA | NSCLC | Antigen-specific immune responses against ≥1 antigen were induced in 65% of pat. ≥ 2 fold increase of pre germinal center B cells; no objective clinical responses follow up trial terminated due to low recruitment | NCT01915524 [163] |
PSA, PSCA, PSMA, and STEAP1 | Vaccine containing self-adjuvanted mRNA | PCA | 26/33 evaluable pat. Treated developed an immune response, directed against multiple antigens in 15 out of 33 pat. One pat. Showed a confirmed PSA response. In the subgroup of 36 metastatic patients, the Kaplan-Meier estimate of median overall survival was 31.4 months | EudraCT number 2008-003967-3 7[164] |
Multiple TAAs | DC | PCA | The addition to of docetaxel to dcvac was safe. Immune responses were detected in approx. Half of the pat. No effect on PFS and DSS | [165] |
Autologous tumor-mRNA | DC | Melanoma | A tumor-specific immune response was demonstrated in 16/31 pat. The response rate was higher after intradermal than intranodal vaccination (80% vs. 38%). Immune responders had improved survival compared to non-responders (median 14 mo vs. 6 mo; p = 0.030), and all 8 pat. Surviving >20 mo were immune responders. | NCT01278940 [166] |
Cancer stem cell mRNA | DC | Glioblastoma | An immune response induced by vaccination was identified in all 7 pat. Compared to matched controls, progression-free survival was 2.9 times longer in vaccinated patients (median 694 vs. 236 days, p = 0.0018, log-rank test). | [167] |
CEA | DC | CRC | All patients showed T-cell responses against the control protein (keyhole limpet hemocyanin) upon vaccination. CEA peptide-specific T-cells were detected in 8 /11 pat. In the peptide group, but in 0/5 patients in the RNA group. | NCT00228189 [168] |
Tyrosinase and gp100 | DC | Melanoma | One mixed tumor response and two durable tumor stabilizations were observed among 8 pat. With evaluable disease at baseline | NCT01530698 [169] |
Total tumor RNA | Naked | Melanoma | Increase in antitumor humoral immune response was seen in some patients after i.d. Injection of naked mRNA. However, a demonstration of clinical effectiveness of direct injection of mRNA for antitumor immunotherapy was not shown in this study and must be evaluated in subsequent trials. | [106] |
Melan-A, gp100, Tyrosinase, Mage-A1, Mage-A3, and survivin in 21 | Protamine-stabil. mRNAs | Melanoma | A reproducible increase of vaccine-directed T cells was observed in 2/4 immunologically evaluable patients. 1/7 pat. With measurable disease showed a complete response. In conclusion, we show here that direct injection of protamine-protected mRNA is feasible and safe | NCT00204607 [170] |
MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1 | I.d. mRNAs | Metastatic RCC | Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients). Long-term survivors displayed immunological responses to the applied antigens while no patient without detectable immune response had survived more than 33 mo. | |
4 Melanoma associated non-Mutated antigens | I.v. mRNAs | Melanoma after CPI | Lipo-MERIT trial: melanoma fixvac, alone or in combination with CPI, mediated durable objective responses in melanoma pat. After CPI treatment. Responses are closely associated with strong CD4+ and CD8+ T cell responses against the vaccine antigens. | NCT02410733 [171] |