PhageKiss: Modular Phage Vector Platform for Sonodynamic Therapy

The technology is a phage vector platform capable of mediating selective ablation of cancer cells or pathogenic bacteria in sonodynamic therapy applications. The phage vector, itself harmless to host cells, is decorated on the surface with hundreds of molecules that produce reactive oxygen species cytotoxic to the target cell, only upon exposure to ultrasound. The same vector can then be easily engineered to expose different cell-specific ligands to target in principle any type of cell/pathogen.

Sonodynamic therapy (SDT) is an innovative therapeutic approach involving a combination of ultrasound and specialized chemical agents known as sonosensitizers. Activation of the sensitizer by ultrasound generates reactive oxygen species (ROS) responsible for cytotoxicity. Because ultrasound can penetrate deeper into tissues than light irradiation, it allows treatment even in deep regions of the body. As an example, ultrasound can be focused on a region of a tumor to activate a sonosensitizer, thus offering the possibility of targeting solid tumors.

One of the limitations strongly felt with SDT, however, is related to the high ultrasound powers that must be employed to achieve enough sensitizer activation to be effective. Conversely, excess ultrasound power also damages healthy tissue. In addition, the sensitizers must be selectively targeted to target cells so as not to damage surrounding healthy cells. A solution (vector) that would allow low ultrasound powers to be combined with specific targeting of a sufficient number of sensitizers would therefore have a disruptive impact in the field of SDT, with a truly wide court of applications and patients benefiting from the advantages offered by the solution.

The applications of the technology are plentiful and lend themselves to personalized medicine approaches. Currently, the development idea is to prioritize anticancer therapies for HER2-positive, EGFR-positive, and GD-2-positive neoplasms that are resistant to chemotherapy and immunological treatments; specifically for the treatment of breast cancer (Her2-positive), ovarian cancer (EGFR-positive, more than 150,000 deaths each year in industrialized countries), epithelioid sarcoma (EGFR-positive), and childhood neuroblastoma (GD-2 positive).

The solution advantageously makes use of intensive conjugation of the M13 phage, because the viral capsid is much larger and more ordered than the surface of antibodies usually used for targeting in SDT, and it can be decorated with a larger number of sensitizers than other therapeutic vectors. The efficiency of SDT is thus increased by at least two orders of magnitude compared with the use of the same nonphage-conjugated sensitizer. The vector design scheme thus has the advantage of increasing the number of sensitizers carried per single binding event, making the application suitable for the use of common ultrasound or phage sonicators, which are already available in the clinic.