Table 1.
Preclinical studies with mRNA vaccines against breast cancer models
| Vaccine type | Target antigen or agonist | RNA modification | Dosage of mRNA | Route of administration | Combination therapy | Disease and treatment models | Results | References |
|---|---|---|---|---|---|---|---|---|
| SAM vaccine (alphaviral vector) | HER2 | NA | 1 × 107 particles/mouse | Footpad injection | NA | BALB/c mice immunized with vaccines before or after implantation of hHER2+ tumor cells | 1. Vaccination-induced HER-2 specific T cells and antibodies | Crosby (2019) |
| 2. Vaccination provided a long-lasting protective effect against tumors and was related to a systemic expansion of CD8+ memory T cells | ||||||||
| LNP mRNA vaccine | MUC1 | Modified nucleotides: 5-methylcytidine-5’-triphosphate, pseudouridine-5’-triphosphate | NA | s.b | Anti-CTLA-4 mAb | BALB/c mice were treated with a vaccine with CTLA-4 blockade after implantation with TNBC 4T1 cells | 1. Vaccine modified with a mannose reached draining lymph node | Liu (2018) |
| 2. Vaccination induced a strong, antigen-specific CTL response against 4T1 cells | ||||||||
| RNA cap: 3’-O-Me-m7G (5’) ppp (5’) G | 3. Combination therapy significantly enhanced the anti-tumor responses with increased CD8+ TIL | |||||||
| DC vaccine | HER-2/neu | NA | NA | NA | Cotransfection with 4-1BBL | In vitro induced HER-2/neu-specific CTLs incubated with DC vaccine | 1. Vaccination increased tumor-specific CTL responses | Grunebach (2005) |
| DC vaccine | p53 | NA | NA | NA | NA | Primary diagnosed BC patients treated with vaccine | 1. Vaccination induced stronger p53-specific T-cell responses in P53high BC patients | Met (2011) |
| SAM vaccine (measle viral vector) | CEA (just as a marker) | NA | 1.2 × 107 TCID50/mouse | i.v | NA | BALB/c nude mice immunized with vaccines after implantation of MDA-MB-231 cells | 1. Vaccination brought significant cytopathic effects consisting of extensive syncytia formation and massive cell death | McDonald (2006) |
| 2. Vaccination significantly delayed tumor growth and prolonged survival | ||||||||
| ISV | Alphavirus vector expressing IL-12 | NA | 5 × 109 viral particles/mouse | i.t | Attenuated Salmonella | BALB/c mice were treated with vaccine before/after attenuated Salmonella after implantation with TNBC 4T1 cells | 1. Vaccination inhibited tumor growth, prolonged survival, reduced angiogenesis, and lung metastasis | Kramer (2015) |
| 2. The combined therapy was markedly synergistic when the vaccine was administered previous to attenuated Salmonella |
4-1BBL 4-1BB ligand, CEA carcinoembryonic antigen, CTLA-4 cytotoxic T lymphocyte-associated antigen-4, DC dendritic cell, HER2 human epidermal growth factor receptor 2, IL-12 interleukin 12, ISV in situ vaccine, i.t. intratumoral injection, i.v. intravenous injection, LNP lipid nanoparticle, MUC1 mucin 1, NA not applicable, SAM self-amplifying mRNA, s.b. subcutaneous injection, TCID tissue culture infective dose