Global population aging is unprecedented: the global population of children under age five is expected to fall by 49 million by midcentury, while the number of people over age 60 will grow by 1.2 billion, according to the United Nations. An aging population brings with it increased demands on healthcare systems. Governments have to reduce healthcare costs while maintaining quality of life. Today, illnesses are treated according to symptoms, but, in the future, with the help of lasers it will be possible to detect and cure illnesses before their critical phase and, hence, cut the high costs of hospitalization.
Screening and medical imaging methods based on photonics will strengthen preventive medicine and the early detection of diseases. Non-invasive or minimally invasive treatments, such as therapeutic laser systems, will help to improve patients’ quality of life and mobility.
Photochemical Internalization Helps in Cancer Therapy
Lasers are increasingly being deployed in the medical field from surgery to non-invasive therapeutic procedures. Semiconductor lasers are wavelength versatile and offer a high level of customization of the output power and beam delivery. One of the most recent application deploying lasers is cancer therapy using a unique photochemical drug delivery technology called photochemical internalization (PCI), developed and patented by PCI Biotech, Oslo, Norway.
PCI is a technology for light-directed intracellular drug delivery by triggered endosomal release. It was developed to introduce therapeutic molecules in a biologically active form specifically into diseased cells. This proprietary technology can provide local enhancement of a range of different drugs, including several cancer drugs currently in clinical use. An essential part of the treatment process is the single-wavelength multi-channel laser source that is used to activate the PCI process. The wavelength and the dose of the laser light in the treated tissue must be carefully controlled and requires designing and building a stable laser system at the desired 652nm photosensitizer wavelength.
PCI Biotech chose to use a medical laser system platform by Modulight, Tampere, Finland, for the PCI treatment process. This demanding treatment process set the bar even higher for an experienced laser system designer like Modulight and served as an excellent case study to assess the performance of state-of-the-art medical lasers.
PCI Biotech is focused on the clinical development of the proprietary photosensitizer Amphinex® in combination with cancer drugs for localized cancer treatment. Amphinex is currently developed in combination with the generic cytotoxic agent bleomycin for head and neck cancer and the generic cytotoxic agent gemcitabine for bile duct cancer. In addition, PCI Biotech has an ongoing pre-clinical program for the use of PCI to enhance the effect of vaccines, with an aim of starting a clinical study next year. A Phase I/II study of Amphinex in combination with bleomycin in cancer patients was completed at the University College Hospital in London, where 19 patients were treated. A strong response to treatment was seen in all patients, and Amphinex seems to be well tolerated.
In 2012, PCI Biotech started to include patients in a Phase II study of Amphinex induced PCI of bleomycin to treat head and neck cancer patients (the ENHANCE study). The ENHANCE study will include approximately 80 patients in 2012 and 2013, targeting patients with recurrent head and neck squamous cell carcinoma unsuitable for surgery and radiotherapy and without distant metastases. PCI Biotech aims to improve the patients’ quality of life, and prolong overall survival. In addition, the treatment may provide an excellent cosmetic outcome.
In Figure 1, a diagram shows that the photosensitizer Amphinex (s) locates to the membranes of intracellular endosomes. A drug (D) taken up by the normal cellular process called endocytosis is trapped in endosomes and can not reach the intracellular targets needed to elicit the therapeutic response. The integrity of the endosomal membrane is disrupted when Amphinex (s) is activated by 652 nm laser light, and the drug (D) can then escape the endosome and reach its intracellular target.
A Proof of Concept study for the use of PCI in patients with bile duct cancer will start in 2013. The Proof of Concept study will include up to 45 patients to assess the safety of Amphinex induced PCI of gemcitabine in patients with inoperable bile duct cancer, a patient population in great need of better treatment options.