Therapeutic tumor vaccines — a rising star to benefit cancer patients

Table 2 Typical mRNA-based tumor vaccines

Vaccine	mRNA-encoded antigen	Formulation type	Disease	NCT ID	Phases	Status	Sponsor/collaborator	Results
mRNA-2416	OX40L	LNP	Relapsed/Refractory Solid Tumor Malignancies or Lymphoma Ovarian Cancer	NCT03323398	Phase I/II	Recruiting	ModernaTX, Inc.	Any dose of intratumoral injection is tolerable when mRNA-2416 is administered alone. Results indicate increased OX40L protein expression, elevated PD-L1 levels and pro-inflammatory activity after mRNA-2416 injection
mRNA-2572	OX40L, IL-23, IL-36γ	LNP	Dose Escalation: Relapsed/Refractory Solid Tumor Malignancies or Lymphoma Dose Expansion: Triple Negative Breast Cancer, Head and Neck Squamous Cell Carcinoma, Non-Hodgkin Lymphoma, and Urothelial Cancer	NCT03739931	Phase I	Recruiting	ModernaTX, Inc., AstraZeneca	Any dose of intratumoral injection is tolerable when mRNA-2572 is administered alone or in combination with PD-L1 inhibitor. IFN-γ, TNF-α, and PD-L1 levels increased
mRNA-4157 KEYNOTE-603	Neo-Ag	LNP	Solid Tumors	NCT03313778	Phase I	Recruiting	ModernaTX, Inc., Merck Sharp & Dohme Corp.	All tested doses is tolerated, and clinical responses were observed when mRNA-4157 is combined with Pembrolizumab
KEYNOTE-942	Neo-Ag	LNP	Melanoma	NCT03897881	Phase II	Recruiting	ModernaTX, Inc., Merck Sharp & Dohme Corp.	Not available
mRNA-5671/Merck V941	KRAS mutations: G12D, G12V, G13D, G12C	LNP	NSCLC, Pancreatic cancer, Colorectal cancer	NCT03948763	Phase I	Recruiting	Merck Sharp & Dohme Corp.	Not available
FixVac (BNT111); Lipo-MERIT	NY-ESO-1, MAGEC3, tyrosinase, TPTE	Lipo-MERIT, LNP	Melanoma	NCT02410733	Phase I	Active, not recruiting	BioNTech SE	BNT111 alone or in combination with PD1, mediates durable objective responses in CPI-experienced patients with unresectable melanoma. Durable clinical responses in both monotherapy and combination with CPI are accompanied by the induction of strong CD4+ and CD8+ T cell immunity. BNT111 vaccination was safe and well tolerated with no dose limiting toxicity
RO7198457 (BNT122)	Neo-Ag	Lipo-MERIT, LNP	Melanoma, NSCLC, Bladder Cancer, CRC, Breast Cancer etc.	NCT03289962	Phase I	Recruiting	BioNTech, Genentech	The combination of RO7198457 and atezolizumab is generally well tolerated. RO7198457 combined with atezolizumab can induce pro-inflammatory cytokine release and peripheral T cell response in most patients
	Neo-Ag	Lipo-MERIT, LNP	Advanced Melanoma	NCT03815058	Phase II	Recruiting	Genentech, Inc., BioNTech SE	Not available
	Neo-Ag	Lipo-MERIT, LNP	Stage II and III CRC (surgically resected)	NCT04486378	Phase II	Recruiting	BioNTech SE	Not available
	Neo-Ag	Lipo-MERIT, LNP	Pancreatic Cancer (surgically resected)	NCT04161755	Phase I	Recruiting	Memorial Sloan Kettering Cancer Center, Genentech, Inc.	Not available
	Neo-Ag	Lipo-MERIT, LNP	NSCLC	NCT04267237	Phase II	Withdrawn	Hoffmann-La Roche	Not available
SAR441000 (BNT131)	IL-12sc, IL-15sushi, IFNα and GM-CSF	Various formulations	advanced melanoma	NCT03871348	Phase I	Recruiting	Sanofi, BioNTech RNA Pharmaceuticals GmbH	Not available
RiboMab (BNT141)	mRNA encoding secreted IgG antibodies that target multiple epithelial solid tumors	Various liver-targeting LNP formulations	CLDN18.2-positive Solid Tumors	NCT04683939	Phase I/II	Not yet recruiting	BioNTech SE	Not available
IVAC MUTANOME, RBL001/RBL002	Neo-Ag/TAA	naked mRNA	Advanced Melanoma	NCT02035956	Phase I	Completed	BioNTech RNA Pharmaceuticals GmbH, BioNTech SE
CV8102	TLR7/8/RIG-1 agonist based on noncoding single stranded RNA	RNActive, (Protamine)	Melanoma (Skin), Squamous Cell Carcinoma of the Skin Carcinoma, Squamous Cell of Head and Neck Carcinoma, Adenoid Cystic	NCT03291002	Phase I	Recruiting	CureVac AG, Syneos Health	Not available
	Peptide vaccine and mRNA	IMA970A plus CV8102 and Cyclophosphamide	Hepatocellular carcinoma	NCT03203005	Phase I/II	Completed	National Cancer Institute, Naples, immatics Biotechnologies GmbH, CureVac AG, European Commission-FP7-Health-2013- Innovation-1	Not available
BI-1361849 (CV9202)	NY-ESO-1, MAGE-C2, MAGE-C1, survivin, 5 T4, MUC1	RNActive, Protamine	Metastatic NSCLC	NCT03164772	Phase I/II	Active, not recruiting	Ludwig Institute for Cancer Research, Cancer Research Institute, New York City; Boehringer Ingelheim, MedImmune LLC, CureVac AG, PharmaJet, Inc.	CV9202 was well-tolerated, and antigen specific immune responses were detected in majority of patients (84%)
CV9201	MAGE-C1, MAGE-C2, NY-SEO-1, survivin,5 T4	RNActive, Protamine	Stage IIIB/IV NSCLC	NCT00923312	Phase I/II	Completed	CureVac AG	CV9201 was well-tolerated and results indicated immune responses after vaccination. Median PFS and OS were 5 and 10.8 mo, respectively
CV9103	PSA, PSCA, PSMA, STEAP1	RNActive, Protamine	Prostate cancer	NCT00831467	Phase I/II	Completed	CureVac AG	CV9103 is well tolerated and immunogenic
CV9104	PSA, PSCA, PSMA, STEAP1, PAP, MUC1	RNActive, Protamine	Prostate cancer	NCT01817738	Phase I/II	Terminated	CureVac AG	Terminated due to insufficient activities

LNP: Lipid Nanoparticle; Neo-Ag: Neoantigen; IFN-γ: Interferon-γ; TNF-α: Tumor necrosis factor-α; PD-L1: Programmed death-ligand 1; IL: Interleukin; GM-CSF: Granulocyte-macrophage colony stimulating factor; NSCLC: Non-small cell lung cancer.