7 Nanomolecular Delivery Accumulation of sensitizer in skin of Bufo Marinus with nanomoleculeSame sensitizer and same dose without nanomolecule formula
8 Gentle Death High dose: necrosis Minimum dose: apoptosis Sensitiser bound to mitochondrial membraneCleave Bcl-2 / Bcl-XLLoss of mitochondrial membrane potentialProgrammed cell death follows
9 S. S. Stylli and A. H. Kaye, J. Clin. Neurosci. 13, 709-717 (2006) PDT of CancerBarret’s OesophagusAdjunct therapy for solid tumoursSystemic administrationNon-surgical debulkingKilling microscopic remnantsTopical application for non-melanoma SCGlioblastoma Multiforme at RMH50% survival at 10 yr, vs ~5% at 2 yr chemoS. S. Stylli and A. H. Kaye, J. Clin. Neurosci. 13, (2006)
10 PDT Causes in-situ Vaccination Adaptive immunity frequently observedRemote metastases controlled / eliminatedTc / NK cells, macrophagesAnimal models resistant to rechallengeAdoptively transferableInflammation due to necrosis, immune response due to apoptosis?F.H. van Duijnhoven et al., Immunobiol. 207, (2003).
11 Activating the Immune System Because PDT creates a perfect vaccination against the cancer in the patients body, the immune system immediately begins to attack the cancer.With antibody therapy the suppressor t-cells are activated.When killing a large tumor up to 95% of the bodies white cells rush to attack the cancer
12 Disabling the DefenseCancer mounts a defense against the immune system.T-cells are converted to suppressor cells which suppress new TIL.Immature myeloid cells are converted to suppressors via ROS.Antibodies disable the defense systems mounted by cancer to enable immune attack
13 Risk Factors with PDTHigh level necrotic kills can cause swelling and inflammation- severe risk for brain tumors.Even with apoptotic kills the amount of cancer killed can be huge.Toxin load can be challenging for hepatic and renal elimination, so maintainance of organ health is vital.
17 Lymphatic Involvement When cancer is not present in lymph nodes, no fluorescence is seen, as in the left picture above.When cancer is present, photodynamic fluorescence is very obvious. A few minutes of laser will resolve this condition.
18 Metastatic Bone Cancer Patient 2: metastasis in the manubriumBefore Treatment After Treatment
23 Psoriasis Active leukocytes accumulate sensitiser Topical PDT of skin autoimmune disordersPsoriasis treated with our sensitiserTwo weeks later
24 Scleroderma treated with our sensitiser Scleroderma Treated over two years agoNo indication of return to dateScleroderma treated with our sensitiser
25 Multiple Sclerosis Before treatment After treatment Multiple Sclerosis treatment is remarkably easy. A one hour infusion with laser illumination at the same time resets the immune system resulting in long lasting remission of symptoms
26 Diabetes Diabetes Mellitus type I has been treated in animal models. Mice genetically programmed to develop DM I treated with PDT have a 60% lower chance of developing DM I.Both types of Diabetes are now being considered as autoimmune diseases.In one diabetic patient treated for cancer, blood sugar levels dropped from 10+ to six range within days after treatment.
27 Diabetic Wound Healing Wounds which normally don’t heal for days or weeks can be treated with a topical application of sensitizer and a few minutes of laser. Wound healing proceeds normally after treatment
28 Bacteria Golden Staph has been tested to 20 generations of LD 50 kills It has never shown indication of developing resistance to PDT.PDT for golden staph can be delivered fast and cost effectively.In Staph from recent injuries or surgeries, the sensitizer can be administered topically and will absorb through the wound.Bloodborne golden staph can be treated with IV infusions.
29 Conclusion PDT: a clinical reality in most developed countries But Australia is trailing ~15 years behindNo sensitiser approved for systemic useLocally developed and manufactured:Portable laser, >5W at present and >10W plannedPhotosensitisers: systemic, intratumoural, topicalIR camera and uniform illumination