Exosomes and their potential application in immunotherapy

Active immunotherapy with mature DCs is being extensively tested for treatment of malignancies. DC-based immunotherapy, however, remains difficult to handle for scale up, definition of quality control parameters, and long-term storage. Indeed, many investigators have shown that one leukopheresis enables up to 4-10 DC injections, whereas there is evidence that a larger number of injections, perhaps spanning over a year or more, appear to be required for long-lasting antitumor protections. Maturation of DCs has been shown to be necessary for efficient DC migration and Tc1 differentiation in lymph nodes. However, GMP cytokine cocktails, required for efficient maturation of DCs need to be, more broadly defined. Finally, regulatory authorities' criteria for the development of therapeutics require biochemical or functional characterization of off-the-shelf products that cannot be readily achieved.

Exosomes might be helpful to overcome part of the shortcomings related to technical development of DCs. Exosome composition can be defined, MHC class I and II content can be measured, and exosomal membranes are stable and can be stored for at least 6 mo. Preclinical studies aimed at demonstrating exosome immunogenicity in vitro and in vivo will be presented as well as the pioneering phase I clinical trial.

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