Exosomes are biological “nanoballs”, between 30-100 nanometers in size and surrounded by a protective lipid bilayer. They are secreted by cells under normal and pathological conditions, and contain proteins and nucleic acids such as mRNA, miRNA and double stranded DNA, which can be shuttled from one cell to another, affecting the recipient cell's protein production.
Tumor exosomes contain the genetic and protein fingerprints of the cancer they are shed from, which means they include all the mutations and markers that are specific to the malignancy. In addition, they contain factors that help the tumor grow and metastasize. Exosomes are shed into body fluids such as blood, urine, cerebral spinal fluid, pleural fluid and ascites and may be retrieved for use in vaccines. With disease progression, increasing concentrations of exosomes are found in these biological fluids.
Cancers are polymorphic, and tumor fingerprints, such as those found in exosomes, typically evolve and change over the course of the cancer’s progression. The use of exosomes as the genetic material for arming the immune system allows the therapeutic vaccine program to be constantly revised against the changing genome of the cancer over time, adding a distinct advantage to ExoCyte’s therapeutic strategy.
Importantly, exosomes have the full neoantigen repertoire of their malignant origin. Neoantigens are the new genetic markers that rapidly evolve in growing malignancies as they mutate. Other strategies to capture the neoantigens from cancer patients rely on tissue biopsies to create therapies. These biopsies represent only a small snapshot of the cancer, are difficult (and sometimes impossible) to obtain, and the use of biopsies to generate personalized immunotherapies relies on expensive and time-consuming gene sequencing, neoepitope construct production, and imperfect algorithms to select what is relevant. Exosomes, by contrast, contain all the protein and genetic neoantigen fingerprints from primary and metastatic tumors in a package that may stimulate a more broad immune response than biopsy material.