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Expert view: GenScript’s unique four-tier platform for successful synthesis of challenging neoantigen peptides for precision medicine

Posted: 1 June 2020 | | No comments yet

Despite hundreds of off-the-shelf treatments, cancer remains the second leading cause of death globally.

Given this drastic statistic, researchers are developing personalised immunotherapies that, as opposed to one-size-fits-all approaches, train a patient’s immune system to attack and kill their own cancerous tissue based on individualised tumour biomarkers known as neoantigens. Unlike common tumour-associated antigens, neoantigens are only expressed in cancer and are therefore highly immunogenic.

A key reagent required for personalised immunotherapy are neoantigen peptides as they are utilised in initial therapeutic candidate discovery, drug development and post-clinical efficacy screening. Unfortunately, generating neoantigen peptides can be cumbersome as neoantigens are often highly hydrophobic, vary in length and charge and require stringent quality control. Despite these inherent challenges, clinicians require these reagents to be developed quickly, as patients receiving these therapies require them urgently. Therefore, GenScript has created a platform for synthesising difficult neoantigen peptides with a 95 percent success rate.

Each neoantigen peptide sequence is entered into GenScript’s proprietary NeoPreTM bioinformatics algorithm, which determines difficulty of synthesis and recommended synthetic technology based on each peptide’s intrinsic characteristics. A peptide expert will then review the algorithm’s results and determine the appropriate synthetic methodology, ranging from liquid phase, solid phase, automated microwave, recombinant expression and/or ligation. In step three, each peptide goes through GenScript’s AccuPepTM quality control analysis, including RP-HPLC, LC-MS and solubility testing. Lastly, the neoantigen sequence is optimised by seven different library design tools, such as alanine scanning and overlapping libraries.

GenScript’s platform provides the technical means and experience to synthesise large numbers of challenging neoantigen peptides, speeding up the timeline and enhancing the efficacy of personalised cancer vaccines and T-cell therapies generated from 50 of the world’s leading immunotherapy organisations.