Utvikling av fotokjemisk internalisering for bruk til å forbedre effekten av terapeutiske og profylaktiske vaksiner.

Photochemical internalisation (PCI) is a technology for light-induced drug delivery that e.g. can be used for enhancing the effect of cytotoxic anti-cancer drugs, a therapeutic principle that is under clinical development for the treatment of patients with bile duct cancer. The PCI technology employs a light sensitising compound (a photosensitiser) that makes cells in the body sensitive to illumination in a way that can induce the release of drug molecules inside illuminated cells; this can lead to increased effect of these drugs. PCI's mechanism of action can also be used to enhance the effect of various types of vaccines by releasing the active component of the vaccine (the antigen) inside some specialised cell types in the immune system; enhancing the ability of these cells to induce beneficial immune responses after vaccination. The PCI technology is especially effective for stimulating so-called ?killer? T-cells, the immune cells in the body that are most effective in eliminating cancer or virus infected cells. The effect of PCI is especially well suited for enhancing the effect of therapeutic cancer vaccines, vaccines that are given with the goal of curing disease in already sick patients. About 300 therapeutic vaccines have been tested in cancer patients, but unfortunately, so far only one such vaccine has reached the market, most other vaccines tested in clinical studies have failed because of too low efficacy. It is therefore a large market potential for technologies, like PCI, that has the potential to improve the effect of such vaccines. For use in vaccination, PCI Biotech's photosensitiser can be mixed with the vaccine before injection into the skin or into a tumour, followed by illumination of the injection site to induce the PCI effect. Experiments in the project have shown that the employment of PCI in such vaccination can significantly enhance the immune response to several types of experimental vaccines in mice. Thus, in some experiments a more than 100 times improvement of the immune response has been observed. Experiments in the project have also shown that PCI can act synergistically with several other immune-stimulating agents. Such agents are used in most ot the cancer vaccines that are under development, and based on the results in the project a patent application has been filed on the use of PCI in combination with such agents. Experiments in mouse models for melanoma and cervical cancer have shown that PCI-based vaccination both in skin and in tumours can generate immune responses that leads to improved tumour treatment; and that in the best cases can cure the animals and make them immune to later challenge with the tumour cells. The very good results achieved in animal studies with PCI-based vaccination have made it possible, and very important, to explore the use of the technology also in humans. Hence, a clinical study with vaccination of healthy volunteers was started in the autumn 2016. In this study, the study subjects are vaccinated in the skin with two types of model vaccines, and a main goal of the study is to find out if PCI-based vaccination can be performed in humans without generating unacceptable side effects. It is also a main goal to see if the use of PCI gives a better vaccination effect than what can be achieved with the same vaccine used without PCI. This will be analysed by various immunological assays on blood samples taken from the study subjects at different time points before and after vaccination. The results from this study are not yet available, but it is expected that preliminary results will be available within a few months. Vaccines formulated as particles may in many cases be more effective than vaccines based on a mixture of soluble single components (like the vaccines described above). As part of the project, the PCI technology has therefore also been tested with particle-based model vaccines. Experiments in mice with some types of particle-based vaccines have given promising results, and will be followed up by further research in this area. Preliminary experiments with using PCI for enhancing the effect of vaccines against infectious diseases have been performed with promising results, e.g. with antigens used in vaccination against hepatitis B virus and tuberculosis. This will be followed up in further studies.

Fotokjemisk internalisering (PCI) er en teknologi for lysindusert legemiddellevering som bl.a. kan brukes til å forsterke og målrette effekten av cellegiftbehandling mot kreft, et behandlingsprinsipp som er under klinisk utprøving. I PCI-teknologien bruk es det lyssensibiliserende stoff (fotosensitiser) som gjør cellene i kroppen følsomme for lys på en slik måte at belysning fører til frigjøring av legemidler inni cellene, noe som vil gi en økt effekt av disse legemidlene. PCIs virkningsmekanisme kan også utnyttes for å øke effekten av visse typer vaksiner ved at den aktive komponenten i vaksinen (antigenet) frigjøres inni spesielle celletyper i immunsystemet, som derved blir i stand til mer effektivt i sette i gang de ønskede immunresponser etter vaksine ring. Ved bruk av PCI til vaksinering vil fotosensitiseren bli injisert sammen med vaksinen i huden, som deretter blir belyst. PCIs virkningsmekanisme er spesielt relevant for å forbedre effekten av terapeutiske kreftvaksiner, men teknologien har også et stort potensial for å brukes sammen med flere typer profylaktiske vaksiner mot infeksjonssykdommer. Selv om det er opp mot 300 kreftvaksiner som er i klinisk utprøving, har bare én kommet på markedet; og mange slike vaksiner har feilet under klinisk utpr øving pga. for dårlig effekt. Det er derfor mange firmaer som er interessert i å betale for teknologier som kan forbedre effekten av slike vaksiner. Innledende forsøk i et modellsystem har indikert at PCI har potensial for å gi en kraftig forbedring av ef fekten av slike vaksiner og hvis teknologien kan optimaliseres og gjøres mer robust, og resultatene kan dokumenteres i klinisk relevante modeller, bør PCI-teknologien være meget attraktiv for mange av de firmaene som utvikler vaksiner. I dette prosjektet er målet å utvikle bruk av PCI for vaksinering videre fram til kommersialisering ved å framskaffe data for bruk til å tiltrekke seg lisenstakere, «file» nye patentsøknader og utvikle nye produkter på dette området.