Filamentous bacteriophages for size, in vivo biodistribution and easiness of engineering, are considered as natural nanoparticles. The developed technology allows the construction of bio-nanoparticles based on filamentous bacteriophages delivering proteic antigens and immunomodulating lipids. Thanks to the high content of hydrophobic residues, phage capsid proteins have high binding affinity to lipids, allowing the conjugation of immunostimulating lipids. Phage particles can also be engineered for the high-density expression of tumor antigen-derived peptides and/or ligands or antibody fragments for the delivery to specific cell subpopulations. We thus conjugated bacteriophages with the glycolipid alpha-GalactosylCeramide and the in vivo administration of these nanoparticles was able to stimulate iNKT cells without inducing anergy, together with a strong adaptive immune response. Therapeutic vaccination with these bacteriophages is able to inhibit tumor growth in animal models.
Bacteriophages replicate only in bacteria and are widely distributed in the environment, making them safe for human use. Their use in therapy against antibiotic-resistant bacterial infections is well-known and currently the object of clinical trials. The use of phages as a vehicle for immunomodulating lipids and tumor antigens for vaccination purposes has not yet been explored and is highly innovative. The proposed technology is focused on the development of innovative and more effective therapeutic strategies to attack cancer cells on several fronts and counteract the mechanisms of escape from the immune response, with the creation of a product that can be used in the fight against oncological diseases combining the pharmacological efficacy with the safety for administration in humans and advantageous production costs. The delivery of aGalCer usingfilamentous bacteriophages exceeds the current limitations of the use of aGalCer in anti-tumor therapy.
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