Table Info

Table 2.

Clinical trials with TAA and neoantigens-based cancer vaccines encoding

Organ	Cancer type/stage	Phases	Cancer vaccine	TAA/neoantigens	Formulation	Study results	Sponsor	NCT number	Reference
Lung	NSCLC Stage IIIB or IV	Phase IIB trial	TG4010	MUC1	TG4010: recombinant modified vaccinia virus strain Ankara (MVA) encoding MUC1 and human interleukin 2 (IL-2)	TG4010 enhances the effect of chemotherapy in advanced NSCLC patients	Transgene SA (France)	NCT00415818	[50]
Lung	NSCLC Stage IIIA vs. IIIB	START study: phase III trial	Stimuvax	MUC1	Tecemotide: MUC1-derived 25-amino acid BLP25 lipopeptide, immunoadjuvant monophosphoryl lipid A, and three liposome-forming lipids	No significant difference in overall survival for all patients	Merck KgaA (Germany)	NCT00409188	[49]
Lung	NSCLC Stage IB, II and IIIA	Phase III trial	MAGE-A3 (AS15 and AS02B)	MAGE-A3	Adjuvant treatment with MAGE-A3	MAGE-A3 immunotherapeutic use in NSCLC has been stopped	GlaxoSmithKline (GSK) Biologicals SA (UK)	NCT00480025	[47]
Lung	NSCLC Stage IB to IIIA	Phase I dose escalation	PRAME (with AS15)	PRAME	PRAME recombinant protein with AS15	Anti-PRAME humoral responses with no cancer regression stopped due to negative results	GSK Biologicals SA (UK)	NCT01159964	[48]
Lung	NSCLC Stage IIIB/IV	Phase II trial	Personalized peptide vaccine with docetaxel	Several TAA	31 Peptides from several TAA	Positive predictive value (PPV) may be efficacious for the humoral immunological responders but did not improve survival in combination with docetaxel for NSCLC patients	Kurume University Research Center for Innovative Cancer Therapy Kurume University School of Medicine (Japan)	UMIN Clinical Trials Registry (UMIN number 000003521)	[53]
Skin	Melanoma Stage IIIA-C/IV	Phase I trial	IVAC mutanome	Multiple neoantigens	Poly-neo-epitopic coding RNA vaccine	Immune responses to the majority of neoantigens contained in the vaccine/vaccine-induced T-cell responses in all vaccinated melanoma patients	BioNTech RNA Pharmaceuticals GmbH (Germany)	NCT02035956	[37]
Lung	NSCLC Stage IV	TIME study: phase IIB/III trial	TG4010	MUC1	TG4010: recombinant MVA encoding MUC1 and human IL-2	TG4010 modulates CD8⁺ T-cell response with improvements in clinical outcome	Not applicable	NCT01383148	[52]
Brain	Glioblastoma Stage IV	Phase I trial	Actively personalized vaccine 1 (APVAC1)	7 Non-mutated peptides, 1 viral peptide, and 2 tumor-associated peptides	APVAC1 vaccine plus poly-ICLC (Hiltonol^®) and GM-CSF	Unmutated APVAC1 antigens elicited sustained responses of central memory CD8⁺ T cells	Immatics Biotechnologies GmbH (Germany)	NCT02149225	[56]
Brain	Glioblastoma Stage IV	Phase I trial	Glioblastoma personalized peptide vaccine (GBM PVax)	8 Synthetic long peptides targeting seven neoantigens	Personalized neoantigen-based long peptide vaccine with poly-ICLC (Hiltonol^®)	Specific T-cell responses in the blood	Washington University School of Medicine (USA)	NCT02510950	[57]
Brain	Glioblastoma Stage IV	Phase I/IB trial	Personalized neoantigen targeting vaccine	20 Long peptides divided into pools of 3–5 peptides admixed with poly-ICLC	Neoantigen vaccine with radiation therapy plus pembrolizumab	Polyfunctional neoantigen-specific CD4⁺ and CD8⁺ T-cell responses exhibiting memory phenotype	Dana-Farber Cancer Institute (USA)	NCT02287428	[58]
Lung	NSCLC Stage IV	Phase II trial	Tedopi^®	5 TAA (CEA, p53, HER2/neu, MAGE2 and MAGE3)	Tedopi plus docetaxel or tedopi plus nivolumab	T-cell response with a better survival rate	OSE Immunotherapeutics (France)	NCT04884282	[54]
Digestive system	Gastrointestinal Stage IV	Phase I/II trial	mRNA-4650	Up to 20 different neoantigens	Neoantigen mRNA-based cancer vaccine	mRNA-4650 vaccine was safe and elicited mutation-specific T-cell responses against predicted neoepitopes	National Cancer Institute (USA)	NCT03480152	[59]
Skin	Melanoma Stage IIIB, C, and IV	Phase I (Lipo-MERIT trial)	FixVac (BNT 111)	4 TAA (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE)	Liposomal RNA (RNA-LPX) vaccine	Strong CD4⁺ and CD8⁺ T-cell immunity against the vaccine antigens/antigen-specific cytotoxic T-cell responses in some responders reach magnitudes and are durable	BioNTech SE (Germany)	NCT02410733	[40]
Lung	Advanced lung cancer Stage IV	Phase I trial	Neo-DCVac	13–30 Peptide-based neoantigens	Neoantigen-pulsed DC vaccine	Neo-DCVac was well tolerated, safe, and capable of eliciting specific T-cell immunity and therapeutic benefit	Sichuan University (China)	NCT02956551 and Chinese Clinical Trial Registry (ChiCTRONC-16009100)	[60]
Skin	Melanoma Stage IIIB/C and IVM1a/b	Phase I trial	NeoVax	Long-peptide vaccine targeting up to 20 personal neoantigens	Neoantigen vaccine with poly-ICLC (Hiltonol^®)	T-cell responses with ex vivo detection of neoantigen-specific T cells exhibiting memory phenotype	Patrick Ott, MD (USA)	NCT01970358	[61]
Brain	Glioma Stage III/IV	Phase I trial	Isocitrate dehydrogenase type 1 (IDH1)-vac	20-Mer peptide-based neoantigens encompassing IDH1R132H-mutated region	IDH1 peptide vaccine with Montanide^®	IDH1 was immunogenic and induces specific T helper cell responses	National Center for Tumor Diseases (Germany)	NCT02454634	[62]
Pancreas	Pancreatic carcinoma Stage IV	Phase I trial	iNeo-Vac-P01	5–20 Peptides-based neoantigens	Neoantigen-based peptide vaccine (iNeo-Vac-P01) with adjuvant (GM-CSF)	No severe vaccine-related adverse effects/higher peripheral IFN-γ titer and CD4⁺ or CD8⁺ effector memory T cells count post-vaccination	Zhejiang Provincial People’s Hospital (China)	NCT03645148	[63]

GM-CSF: granulocyte-macrophage colony-stimulating factor; IFN-γ: interferon-γ

Declarations

Acknowledgments

The authors thank Sarah MacKenzie for editorial help.

Author contributions

MOA, SC and FMC: Conceptualization. MOA and SC: Creation of tables and figures. All authors contributed to the manuscript revision, read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This work was supported by grants from the French Institut National du Cancer (INCa; Grant number PRTK-2020-070); Agence Nationale de la Recherche (ANR-PRCE-2021, ANR-21-CE17-0049-01) and Fondation de France (2021; Grant number 00119144/WB-2021-34171). SC is supported by grants from Association pour la Recherche sur le Cancer (ARC; Grant number SIGN’IT20181007792). MOA is a recipient of a fellowship from Fondation de France (2021; Grant number 00119144/WB-2021-34171). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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