Table 1 |.
Clinical advantages and roadblocks of current and emerging technologies for personalized cancer immunotherapy
| Technology | Clinical advantages | Clinical roadblocks |
|---|---|---|
| Neoantigen peptide vaccines, soluble23–25,27,29,30 | High specificity for individual tumours Applicable to a wide variety of cancers with high mutational load Demonstrated synergy with immune-checkpoint blockade | Imprecise neoantigen prediction tools Time-consuming process for cGMP production Antigen instability or insolubility Relatively weak T-cell immunity elicited |
| Neoantigen peptide vaccines, delivery via nanoparticles16,47,52,56,57 | Enhanced antigen stability and solubility Enables the co-delivery of neoantigens and adjuvants to antigen-presenting cells Elicits strong T-cell responses Synergies with immune-checkpoint blockade | Unique formulation parameters required for each neoantigen-nanoparticle strategy Complex cGMP manufacturing of the nanoparticles Concerns about biocompatibility and safety |
| Gene-based vaccines26,28,85 | Efficient antigen expression and immune activation Synergies with immune-checkpoint blockade | Instability in vitro and in vivo Low transfection efficiency in vivo Unique formulation parameters required for delivery Complex cGMP manufacturing |
| DC-based vaccines90,93 | Based on patient-derived cells Elicits tumour-specific immune responses | Time-consuming-manufacturing process Highly variable yield of antigen-presenting cells No demonstration of complete remission to date Inefficient cellular trafficking to lymph nodes |
| Adoptive T-cell therapies113,121,122 | Based on patient-derived cells Infusion of large numbers of T cells feasible Established procedures for engineering CAR-T cells Effective targeting of tumours | Time-consuming manufacturing process Problems in maintaining T-cell viability Insufficient proliferation and tumour-infiltration of T cells in vivo Limited efficacy when targeting shared antigens |
| Theranostic nanoparticles124,127,138,144 | Site-specific delivery and release of therapeutics Increased permeability of target tissue for efficient delivery Tumour targeting in real time | Costly Requires bulky equipment Concerns about biocompatibility and safety |
| Photothermal- photodynamic and radiation therapies14,17,154–156 | Minimally invasive Effective in large tumours May trigger the release of tumour antigens and elicit endogenous immune responses | Requires combination with other agents Ineffective for metastatic tumours Concerns about biocompatibility and safety |