Progress toward development of photodynamic vaccination against infectious/malignant diseases and photodynamic mosquitocides
| Autor: | Dennis K. P. Ng, Neng Yao Shih, Xiong-Jie Jiang, Chia Kwung Fan, Kwang-Poo Chang, Laura Manna, Shin-Hong Shiao, Robert Elliott, Raffaele Corso, Clarence T. T. Wong, Bala K. Kolli, Guo Liang Fu |
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| Přispěvatelé: | Dai, Tianhong, Chang, K. P., Kolli, B. K., Fan, C. -K., Ng, D. K. P., Wong, C. T. T., Manna, L., Corso, R., Shih, N. -Y., Elliott, R., Jiang, X. P., Shiao, S. -H., Fu, G. -L. |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
photo-inactivation medicine.medical_treatment 030231 tropical medicine 030106 microbiology Photodynamic therapy mouse tumor model singlet oxygen 03 medical and health sciences 0302 clinical medicine Canine leishmaniasis Medicine vaccine safety Lung cancer Leishmania Chemotherapy vaccine carrier biology business.industry Leishmaniasis Immunotherapy vaccination medicine.disease biology.organism_classification Vaccination lung cancer phthalocyanine compassionate trial Cancer research List: Photosensitizer immunotherapy business porphyrin canine leishmaniasi |
| Zdroj: | Light-Based Diagnosis and Treatment of Infectious Diseases. |
| Popis: | Photodynamic therapy (PDT) uses photosensitizers (PS) that are excited with light to generate ROS in the presence of oxygen for treating various diseases. PS also has the potential use as photodynamic insecticides (PDI) and for light-inactivation of Leishmania for photodynamic vaccination (PDV). PDT-inactivated Leishmania are non-viable, but remain immunologically competent as whole-cell vaccines against leishmaniasis, and as a universal carrier for delivery of add-on vaccines against other infectious and malignant diseases. We have screened novel PS, including Zn- and Si-phthalocyanines (PC) for differential PDT activities against Leishmania, insect and mammalian cells in vitro to assess their PDI and PDV potential. Here, Zn-PC were conjugated with various functional groups. The conjugates were examined for uptake by cells as a prerequisite for their susceptibility to light-inactivation. PDT sensitivity was found to vary with cell types and PS used. PDI potential of several PS was demonstrated by their mosquito larvicidal PDT activities in vitro. PDT-inactivated Leishmania were stored frozen for PDV in several ongoing studies: [1] Open label trial with 20 sick dogs for immunotherapy of canine leishmaniasis after chemotherapy in Naples, Italy. Clinical follow-up for >3 years indicate that the PDV prolongs their survival; [2] PDV of murine models with a human lung cancer vaccine showed dramatic tumor suppression; [3] Open label trial of multiple PDV via compassionate access to 4 advanced cancer patients showed no clinically adverse effects. Two subjects remain alive. Genetic modifications of Leishmania are underway to further enhance their safety and efficacy for PDV by installation of activable mechanisms for self-destruction and spontaneous light-emission. Keyword list: Photosensitizer, phthalocyanine, porphyrin, photo-inactivation, singlet oxygen, Leishmania, vaccine carrier, vaccination, immunotherapy, canine leishmaniasis, lung cancer, mouse tumor model, compassionate trial, vaccine safety. |
| Databáze: | OpenAIRE |
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