Table 2 Clinical trials of mRNA vaccine against single tumor

Registration

number

Status

Diseases

Phase

Encoding mRNA

Adjuvants

Delivery Tools

Additional therapies

Outcomes

ref

NCT03394937

Terminated

Melanoma

I

TAA: gp100, tyrosinase, MAGE-A3, MAGE-C2, PRAME

TriMix

Synthetic

naked mRNA

-

Immunologically active cells against cancer were activated and expected potential risks are non-serious and related to the local administration of the product

[53]

NCT01066390

Completed

Melanoma

IB

TAA: either gp100, MAGE-A3, MAGE-C2 or tyrosinase

TriMix

DCs-based

-

15 patients tolerated administration of the vaccine well. Four durable objective tumor responses were observed during a follow-up over 2 years. Antigen-specific skin infiltrating lymphocytes were detected in 6/12 patients

[154]

NCT01676779

Completed

Melanoma

II

No exact details

TriMix

DCs-based

-

71% of patients in TriMix cohort were alive and free of disease compared to 35% in the control cohort after 1 year into the group. 9/21 patients in TriMix cohort experienced a non-salvageable melanoma recurrence compared to 14/20 in the control cohort after a median follow-up of 53 months

[181]

NCT01302496

Completed

Melanoma

Stage III/ IV

II

TAA: tyrosinase, gp100, MAGE-A3, or MAGE-C2

TriMix

DCs-based

Ipilimumab

T-cell responses against antigens were detected in 12/15 patients. Treated patients resulted in an OS of 28% and a PFS of 18% during follow-up over 5 years

[155]

NCT02410733

Active, not recruiting

advanced melanoma

I

TAA: NY-ESO-1,

Tyrosinase, MAGE-A3, TPTE

-

Cationic liposomes

anti-PD1 therapy

Exploratory interim analysis showed that long-lasting antigen-specific CD4/8 + T cell responses were induced and regression of lesions was observed in multiple patients within 300 days of initiation of treatment

[156]

NCT02035956

Completed

Melanoma

Stage III/ IV

I

TSA:

poly-neoepitope;

RBL001/RBL002

-

Naked mRNA

-

T cell response were detected in 60% selected neoepitopes. 75% of the patients had a progression-free survival of 27 months

[159]

NCT01684241

Terminated

Metastatic melanoma

I

TAA:

MART, tyrosinase, gp100, MAGE-3

-

DCs-based

GITR-L,

Anti-CTLA4 mAb

Antigen-specific immune responses against TAAs and survival were enhanced when vaccines combing with GITR-L and anti-CTLA-4 mAb

[153]

NCT00978913

Completed

Melanoma

I

TAA:

hTERT, survivin, p53

-

DCs-based

Cyclophosphamide

Immune responses were detected in 6/17 patients by IFNγ ELISpot and 4/17 patients by proliferation assay. 9/22 treated patients achieved disease stabilization, 3/18 evaluable patients experienced tumor shrinkage

[182]

NCT00243529

Completed

Melanoma

Stage III/ IV

I/II

TAA:

Tyrosinase, gp100

-

DCs-based

-

TAA-specific CD4/CD8 + T cell responses were detected in 17/26 stage III patients and 11/19 stage IV patients. Stage IV patients with TAA-specific CD8 + T cell responses had a median overall survival of about 12 months longer than those who without response

[183]

NCT02285413

Completed

Melanoma

Stage III/ IV

II

TAA:

Tyrosinase, gp100

-

DCs-based

Cisplatinum

44% antigen-specific CD8 + T cells and 28% functional T cell responses were detected in skin infiltrating lymphocytes from vaccinated patients with cisplatin. The relevant data were 67% and 19% for those vaccinated alone

[157]

NCT00204607

Completed

Melanoma

Stage III/ IV

I/II

TAA: gp100,

Melan-A, MageA3, survivin, MageA1, tyrosinase

GM-CSF

Protamine

-

Vaccine-induced T cells were increased in 2/4 immunologically evaluable patients and a complete response was observed in 1/7 patients with measurable disease

[184]

NCT00678119

Completed

Renal cell carcinoma

II

TAA and immune modulators

CD40L

DCs-based

sunitinib

62% patients experienced clinical benefit (9 partial responses, 4 with stable disease), and five patients (24%) survived for more than 5 years

[185]

NCT01890213

Completed

Colorectal Cancer

I

TAA: CEA

-

VRP

-

CEA-specific humoral immunity was observed in all involved patients. For patients with stage IV cancer, 5-year survival was 17%, (95% CI 6% to 33%). For patients with stage III cancer (n = 12), the 5-year RFS was 75%, (95%CI 40% to 91%)

[186]

NCT00228189

Completed

Colorectal Cancer

I/II

TAA: CEA

-

DCs-based

-

The median PFS after mRNA-loaded DCs treatment was 26 months and median PFS for patients with peptide-loaded DCs treatment was 18 months

[187]

NCT02709616

NCT02808364

Completed

GBM

I

TAA:

containing 3–13 different TAAs

-

DC-based

low-dose cyclophosphamide, imiquimod poly I:C, and anti-PD-1 antibody

TAA-specifc CD4 + or CD8 + T cell responses were detected in 2/5 GBM patients. The median survival time was 19 months for the GBM patients

[188]

NCT00846456

Completed

GBM

I/II

GSCs mRNA

-

DC-based

-

For vaccinated patients, the PFS was 694 days; for control group, the PFS was 236 days

[189]

NCT01686334

Recruiting

AML

II

TAA: WT1

-

DC-based

low-intensity chemotherapy

5/10 patients with high WT-1expression showed molecular remission after vaccination, of 2 patients achieved complete remission

[190]

NCT01278940

Completed

Melanoma

I/II

No exact details

-

DCs-based

IL-2

Higher T cell proliferation to transferred DCs (tDC) than mockDC controls were observed in 10/19 patients. tDC-specific response was still detected over 10 weeks after last vaccination in 4/6 patients

[191]

NCT03164772

Completed

NSCLC

I/II

TAA: MAGE-C1、NY-ESO-1、MAGE-C2、survivin、5T4, MUC-1

-

Protamine

Durvalumab, Tremelimumab

Vaccine was well-tolerated, and immune responses against TAAs were detected in majority of patients

[53]

NCT00923312

Completed

NSCLC

I/II

TAA: NY-ESO-1, 5T4, MAGE-C1, MAGE-C2, survivin, MUC-1

-

LNP

-

CV9201 was well-tolerated. Median PFS and OS were 5.0 months (95% CI 1.8–6.3) and 10.8 months (8.1–16.7) since first administration. 2- and 3-year survival rates were 26.7% and 20.7%, respectively

[192]

NCT01915524

Terminated

NSCLC

I

TAA: NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, MUC-1

-

Protamine

Pemetrexed

80% patients had elevated levels of antigen-specific antibodies and 40% had elevated levels of functional T cells. 46.2% patients achieved stable disease

[193]

NCT01446731

Completed

Prostate cancer

II

TAA: PSA, PAP, survivin, hTERT

-

DCs-based

Docetaxel

PFS and OS were 5.5 and 21.9 months, respectively, for patients receiving docetaxel monotherapy and 5.7 and 25.1 months, respectively, for patients receiving combination therapy

[158]

EudraCT number:2008–003,967-37

Completed

Prostate cancer

I/II

TAA: PSA, PSCA, PSMA, STEAP1

-

protamine

-

A cellular immune response was observed in 25/33 of the patients. median OS was 31.4 months [95% CI: 21.2] for 36 treated patients with metastatic prostate cancer

[194]