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Table 1 Clinical results from studies using mRNA vaccines in tumor therapy (extract)

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.

[110, 111]

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]

  1. Abbreviation: RCC renal cell cancer, CRC colorectal cancer, PCA prostata cancer