On January 15, 2020 GenScript, a world leading biotechnology company, reported its support of Avidea Technologies’ efforts to develop a groundbreaking peptide-based personalized cancer vaccine (Press release, GenScript, JAN 15, 2020, View Source [SID1234553248]).
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Research published in Nature Biotechnology on January 13, 2020 describes the systematic development of Avidea’s personalized cancer vaccine (SNP-7/8a) based on a self-assembling nanoparticle technology (referred to as "SNAP"), which was shown to more efficiently induce T-cell responses against tumor neoantigens compared to traditional vaccines. Developing and validating SNP-7/8a as a personalized cancer vaccine required synthesis of hundreds of unique neoantigen peptides, which were successfully synthesized by Genscript in support of this work.
"Screening hundreds of neoantigens in mice to validate the generalizability of SNP-7/8a was a tremendous undertaking that could not have been possible without the diligent efforts of GenScript’s peptide chemists who were able to rapidly synthesize even the most challenging sequences at the high purity required," said Avidea Technologies’ CEO Geoffrey Lynn, PhD, a primary author of the study.
The publication is particularly timely as personalized cancer vaccines are garnering increasing attention among the scientific and medical community as important components to enabling precision immuno-oncology. While traditional cancer treatment is largely based on "one size fits all" approaches such as chemotherapy and radiation, which can be limited by off-target effects and low efficacy for treating certain advanced cancers, precision immuno-oncology promises to reduce off-target toxicity and improve efficacy by training a patient’s own immune response, particularly T cells, to attack cancerous cells.
Key to enabling precision immuno-oncology is focusing the immune response against tumor-specific peptide antigens, particularly neoantigens, which are mutant peptides that are unique to cancerous tissue and are not found in healthy tissue. Current vaccines using neoantigen peptides have shown promise in initiating neoantigen-specific T-cell responses. However, the response itself is often not as robust as may be required for tumor regression, which may be in part due to the inability of conventional vaccine platforms to account for the broad variability of neoantigen peptide properties.
In order to address challenges associated with neoantigen peptide variability, Avidea Technologies, working in close collaboration with the Vaccine Research Center at the National Institutes of Health (NIH), developed a personalized cancer vaccine platform (SNP-7/8a) that ensures any neoantigen peptide, irrespective of the underlying amino acid sequence, can be self-assembled into uniform nanoparticles of an optimal size and composition for inducing T-cell responses.
To support this work, GenScript synthesized hundreds of challenging neoantigen peptides that were selected to have a wide range of properties, including neoantigen peptides with extremes of net charge and hydrophobicity, which was instrumental to enabling Avidea and NIH scientists to validate the generalizability of the SNP-7/8a platform as a personalized cancer vaccine. In order to accomplish these challenging syntheses, the GenScript team utilized their 15 years of experience in complex and hydrophobic peptide synthesis, high throughput LPS/SPS/microwave synthesis platforms, and patented quality control program.
"We are honored that Avidea chose to partner with GenScript to synthesize the hundreds of difficult peptides required for this study. As neoantigens can have quite variable properties, working on this project has strengthened our ability to manufacture large quantities of these difficult peptides," said Xin Zhang, associate director of GenScript’s peptide services. "We look forward to our continued collaboration with Avidea on future breakthrough neoantigen peptide vaccines to advance the precision immuno-oncology field."
Leveraging GenScript’s core strength in difficult peptide synthesis, Avidea and the NIH were able to demonstrate the utility of SNP-7/8a for improving formulation consistency and increasing the magnitude and breadth of neoantigen-specific T-cell responses in mice as compared with two gold-standard cancer vaccine technologies. Additionally, the SNP-7/8a platform was also shown to induce CD8 T-cell responses in non-human primates, which is predictive of responses in humans. Based on these encouraging data, Avidea is planning to advance SNP-7/8a to clinic in 2020.
GenScript was pleased to support these studies and hopes that such efforts and continued cooperation with Avidea and others in this space will lead to more efficacious precision immuno-oncology treatments and ultimately improved outcomes for patients.