Table 1 The different types of mRNA cancer vaccines
From: The use of RNA-based treatments in the field of cancer immunotherapy
mRNA Cancer Vaccine Type | Mechanism of Action | Advantages | Disadvantages | Immunogenicity | Efficacy | Safety | Stability | Reference |
|---|---|---|---|---|---|---|---|---|
DC mRNA cancer vaccines | Direct ex vivo loading of patient-derived DCs | Highly personalized, high antigen expression, long-lasting immune response | Requires specialized personnel and equipment, complex manufacturing, short half-life in vivo | High | High in preclinical studies, moderate in early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short shelf life in vivo | [55] |
Direct injection of mRNA cancer vaccines | Direct injection of mRNA into the tumor or surrounding tissue | Simplicity, low cost, no requirement for specialized personnel or equipment | Low antigen expression, limited potential for systemic immune response, requires multiple injections | Low to moderate | Moderate in preclinical studies, limited in early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [56] |
mRNA cancer vaccines encoding immunostimulants | mRNA encoding for cytokines or other immune system activators | Potent immune stimulation, potential for systemic response | Requires identification and optimization of appropriate immunostimulant, potential for excessive inflammation | High | Moderate in preclinical studies, limited in early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [11] |
mRNA cancer vaccines encoding tumor-associated antigens | mRNA encoding for specific tumor-associated antigens | Highly personalized, specific targeting of tumor cells, potential for long-lasting immune response | Requires identification and optimization of appropriate antigen, limited potential for systemic response | Moderate to high | Moderate in preclinical studies, limited in early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [57] |
mRNA cancer vaccines encoding neoantigens | mRNA encoding for patient-specific neoantigens | Highly personalized, specific targeting of tumor cells, potential for long-lasting immune response | Requires identification and optimization of appropriate neoantigen, limited potential for systemic response | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [58] |
Self-amplifying mRNA cancer vaccines | mRNA encoding for self-amplifying RNA vectors | High antigen expression, potential for long-lasting immune response | Complex manufacturing, short half-life in vivo, potential for excessive inflammation | High | Moderate in preclinical studies, limited in early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [59] |
Lipid nanoparticle (LNP) mRNA cancer vaccines | mRNA encapsulated in lipid nanoparticles for delivery | High antigen expression, potential for systemic immune response, potential for enhanced cellular uptake | Complex manufacturing, potential for toxicity or adverse reactions to LNP, potential for immune recognition and clearance | High | Moderate in preclinical studies, limited in early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [59] |
Peptide-based mRNA cancer vaccines | mRNA encoding for specific peptides | Highly specific targeting of tumor cells, low potential for toxicity or adverse reactions, potential for systemic immune response | Limited potential for long-lasting immune response, requires identification and optimization of appropriate peptide | Low to moderate | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [60] |
Adjuvant-assisted mRNA cancer vaccines | mRNA combined with adjuvants to enhance immune response | Potential for potent immune stimulation, potential for systemic response | Requires identification and optimization of appropriate adjuvant, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [61] |
Non-replicating mRNA cancer vaccines | mRNA encoding for non-replicating viral antigens | Highly specific targeting of tumor cells, potential for long-lasting immune response | Requires identification and optimization of appropriate antigen, limited potential for systemic response | Moderate to high | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [62] |
Nanoparticle-assisted mRNA cancer vaccines | mRNA combined with nanoparticle delivery systems for enhanced uptake | High antigen expression, potential for systemic immune response, enhanced cellular uptake | Complex manufacturing, potential for toxicity or adverse reactions to nanoparticle, potential for immune recognition and clearance | High | Moderate in preclinical studies, limited in early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [63] |
mRNA cancer vaccines with checkpoint inhibitors | mRNA encoding for checkpoint inhibitors to enhance anti-tumor immune response | Potential for enhanced immune response, specific targeting of tumor cells | Limited potential for long-lasting immune response, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [64] |
mRNA cancer vaccines with CAR-T cells | mRNA encoding for CAR-T cells for targeted immune response | Highly specific targeting of tumor cells, potential for long-lasting immune response | Complex manufacturing, potential for toxicity or adverse reactions to CAR-T cells, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [11] |
mRNA cancer vaccines with gene editing tools | mRNA encoding for gene editing tools for targeted modification of tumor cells | Highly specific targeting of tumor cells, potential for long-lasting immune response | Requires identification and optimization of appropriate gene editing tools, potential for off-target effects | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [65] |
mRNA cancer vaccines with adjuvant-loaded exosomes | mRNA combined with exosomes carrying adjuvants for enhanced immune response | High antigen expression, potential for systemic immune response, potential for long-lasting immune response | Requires optimization of appropriate exosome-adjuvant combination, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [66] |
mRNA cancer vaccines with oncolytic viruses | mRNA encoding for oncolytic viruses for targeted destruction of tumor cells | Highly specific targeting of tumor cells, potential for long-lasting immune response | Requires identification and optimization of appropriate oncolytic virus, potential for off-target effects, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [67] |
mRNA cancer vaccines with chimeric antigen receptor (CAR) mRNA | mRNA encoding for CARs for targeted immune response | Highly specific targeting of tumor cells, potential for long-lasting immune response | Complex manufacturing, potential for toxicity or adverse reactions to CARs, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [11] |
mRNA cancer vaccines with bispecific T cell engagers (BiTEs) | mRNA encoding for BiTEs for targeted immune response | Highly specific targeting of tumor cells, potential for long-lasting immune response | Complex manufacturing, potential for toxicity or adverse reactions to BiTEs, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [68] |
mRNA cancer vaccines with multiple antigens | mRNA encoding for multiple tumor-associated antigens | Potentially higher response rates, potential for broad targeting of tumor cells | Requires identification and optimization of appropriate antigens, potential for autoimmune response | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [69] |
mRNA cancer vaccines with personalized neoantigens | mRNA encoding for personalized neoantigens specific to patient's tumor | Highly specific targeting of tumor cells, potential for long-lasting immune response | Requires sequencing and analysis of patient's tumor, potential for autoimmune response, complex manufacturing | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [70] |
mRNA cancer vaccines with cytokine encoding mRNA | mRNA encoding for cytokines to enhance anti-tumor immune response | Potential for enhanced immune response, specific targeting of tumor cells | Limited potential for long-lasting immune response, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [71] |
mRNA cancer vaccines with immune checkpoint inhibitors | mRNA encoding for immune checkpoint inhibitors to enhance anti-tumor immune response | Potential for enhanced immune response, specific targeting of tumor cells | Limited potential for long-lasting immune response, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [2] |
mRNA cancer vaccines with immune-modulatory agents | mRNA encoding for immune-modulatory agents to enhance anti-tumor immune response | Potential for enhanced immune response, specific targeting of tumor cells | Limited potential for long-lasting immune response, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [69] |
mRNA cancer vaccines with immunomodulatory genes | mRNA encoding for immunomodulatory genes to enhance anti-tumor immune response | Potential for enhanced immune response, specific targeting of tumor cells | Limited potential for long-lasting immune response, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [67] |
mRNA cancer vaccines with tumor-derived extracellular vesicles | mRNA combined with extracellular vesicles derived from tumor cells to enhance immune response | High antigen expression, potential for systemic immune response, potential for long-lasting immune response | Requires optimization of appropriate extracellular vesicle-mRNA combination, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [72] |
mRNA cancer vaccines with RNA sensors | mRNA encoding for RNA sensors to activate innate immune response and enhance anti-tumor immune response | Potential for enhanced immune response, specific targeting of tumor cells | Limited potential for long-lasting immune response, potential for excessive inflammation or toxicity | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [73] |
mRNA cancer vaccines with novel delivery systems | mRNA combined with novel delivery systems for enhanced stability and efficient delivery | Potential for enhanced immune response, specific targeting of tumor cells, increased stability and efficiency of mRNA delivery | Requires optimization of appropriate delivery system, potential for toxicity or adverse reactions to delivery system | High | Limited in preclinical studies and early clinical trials | Generally safe, rare cases of autoimmune response | Requires refrigeration or cryopreservation, short half-life in vivo | [74] |