Editorial: Synthetic peptide vaccine platforms targeting tumor-specific antigens: advances and challenges
Year: 2024
Type: editorial
Abstract: Advancements in tools for predicting peptide binding to Major Histocompatibility Complex (MHC) are noteworthy, including the integration of deep learning AI in HLA/peptide combination binding predictors. [1] It is crucial to emphasize that while MHC binding affinity is a valuable screening metric, it alone does not predict immunogenicity: MHC binding is a necessary but not sufficient condition for specific T-cell expansion and to evoke T-cell effector function. [2] We believe that confirmation through in-vivo or in-vitro determination of actual TCR MHC/peptide binding characteristics remains an essential part of peptide vaccine design. This confirmation can be achieved indirectly using techniques such as ELISPOT or directly through newer approaches such as TCR sequencing. [3,4] TLR agonists have also proven to be integral to the latest generation of vaccines. Notably, TLR-4 and TLR-9 agonists have been incorporated into FDA-approved vaccines, significantly improving the immunogenicity of Virus-Like Particle (VLP) and other vaccine designs. [5] The use of TLR adjuvants becomes especially significant in the design of synthetic peptide cancer vaccines, considering that exogenously administered short peptides lack the immunogenicity of larger proteins. [6,7] Addressing this issue, some researchers have opted for single long peptides (SLPs). [8] However, these present challenges as enzyme degradation during antigen processing may cleave SLPs into unintended smaller sequences. [9] Even a minor deviation of one amino acid from the predicted immunogenic peptide sequence by vaccine designers may result in the delivered peptide no longer being immunogenic. [10,11] While mRNA vaccines theoretically enhance the immunogenicity of desired peptide antigen targets by producing peptides within cells via the canonical pathway, recent publications have raised concerns about potential transcription errors inherent to mRNA vaccines. [12,13,14] This could lead to situations similar to those observed with SLPs, where delivered peptides deviate from the intended sequence and become non-immunogenic.Synthetic peptide vaccine platforms offer potential advantages, potentially avoiding the manufacturing complexity and safety issues associated with mRNA vaccines and viral vectors. The tools available for designing peptide vaccines for oncology applications are increasing, holding promise for further developments in the field.
Source: Frontiers in Pharmacology
Authors: Reid M. Rubsamen, Andrew E. Sloan
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,295
OpenAlex ID: W4392108257