Personalized Neoepitope mRNA Cancer Vaccine Platform
Many approaches have been developed for the preparation, formulation, and delivery of different cancer vaccines, including mRNA. Equipped with a team of professional scientists, Creative Biolabs is capable of providing specialized support in the design, production, and evaluation of personalized neoepitope mRNA cancer vaccines to bring your mRNA therapeutics closer to clinical realization. We can accommodate the specific attributes of your project and provide flexible and integrated solutions.
A large number of cancer vaccines prepared from different materials have been studied, such as mRNA or DNA, whole tumor cell lysates, protein or peptides, dendritic cell (DC)-based, viral or bacterial vectors, and so on. In the context of neoantigen-based cancer vaccines, synthetic long peptides (SLP) or mRNA/DNA are commonly used. First Sahin and his colleagues successfully used an individualized new epitope mRNA cancer vaccine. They use high-throughput sequencing to identify each unique somatic mutation in a patient's tumor sample (mutanome), which enables rational design of new epitope cancer vaccines in a patient-specific manner with the advantage of targeting non-self antigen specificity that should not be eliminated by a central tolerance mechanism. In addition, Kreiter and colleagues discovered that most non-synonymous cancer mutations are immunogenic when delivered by mRNA and are primarily recognized by CD4+ T cells. Based on these data, they generated a computational method to predict major histocompatibility complex (MHC) class II restricted new epitopes that could be used as vaccine immunogens. The mRNA vaccine encoding this new epitope controls tumor growth in the B16-F10 melanoma and CT26 colon cancer mouse models.
Fig.1 Schematic illustration of the process of neoantigen discovery, vaccine manufacturing and formulation, and vaccination in patients. (Guo Y. 2018)
Direct Injection of Unformulated mRNA Vaccines Encoding Neoepitopes
In vitro transcription (IVT) mRNA is used for therapeutic cancer vaccination, with the advantages of self-adjuvanting activity, direct translation into cytoplasm, low risk of insertional mutagenesis, and simple and inexpensive manufacturing procedure. However, controlling the translational efficiency of IVT mRNA remains difficult because unconstructed mRNA can be taken up by a variety of cells spontaneously by scavenger receptor-mediated endocytosis. As a result, APC may capture only a small fraction of the administered mRNA which reaches the cytoplasm for subsequent translation and antigen presentation. To ameliorate this shortcoming, unformulated IVT mRNA can be directly injected into LNs by ultrasound-guided percutaneous injection to maximize the capture of antigens by APCs.
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Reference
- Guo Y, et al. Neoantigen Vaccine Delivery for Personalized Anticancer Immunotherapy. Front Immunol. 2018, 9:1499.
All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.
