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Recombinant bacteriophage for Immunotherapy

cancerglycolipid alpha-galactosylceramideImmunotherapyinfectious agentsrecombinant bacteriophage

Introduction

The invention relates to pharmaceutical compositions comprising lipid- bacteriophage conjugates, wherein lipid, as the glycolipid alpha-Galactosylceramide is immunologically active and the bacteriophage is engineered to bind to target cells and carry antigenic molecules capable of stimulating an immune response. Such bacteriophage is used to stimulate an immune response against cancer and against infectious agents.

Technical features

Immunotherapeutic strategies, used in combination, result in better results against cancer . Here we propose the use of natural nanoparticles based on filamentous bacteriophages capable of delivering immunologically active protein and lipid antigens to specific target cells. These lipids bind the phage coat proteins by means of hydrophobic interactions and, using the phage display technology, the bacteriophages are engineered for delivering high copies of tumor antigens. Therapeutic vaccination with such bacteriophages is able to inhibit the tumor growth in animal models, and to increase the survival rate (80% vs control). Furthermore, the technology allows to construct bacteriophages capable of being specifically targeted to different dendritic cell subpopulation, by co-expressing ligands or antibody fragments (ScFv) specific for the membrane receptors of dendritic cells.

Possible Applications

  • Cancer immunotherapy;
  • Immunotherapy against infectious agents.

Advantages

  • Safe administration in humans;
  • Production is simple and economically advantageous;
  • Ability of phage nanoparticles to stimulate innate immunity;
  • Ability to induce a strong adaptive response to the delivered epitopes;
  • Innovative approach to enhance anti-tumor responses.