Progress toward development of photodynamic vaccination against infectious/malignant diseases and photodynamic mosquitocides
Journal
Progress in Biomedical Optics and Imaging - Proceedings of SPIE
Journal Volume
10479
Pages
1047912
Date Issued
2018
Author(s)
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.
Fu G.-L.
Abstract
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. ? 2018 SPIE.
Subjects
canine leishmaniasis; compassionate trial; immunotherapy; Leishmania; List: Photosensitizer; lung cancer; mouse tumor model; photo-inactivation; phthalocyanine; porphyrin; singlet oxygen; vaccination; vaccine carrier; vaccine safety
SDGs
Other Subjects
Biological organs; Cells; Chemotherapy; Cytology; Diagnosis; Disease control; Mammals; Photodynamic therapy; Photosensitizers; Porphyrins; Silicon compounds; Tumors; Vaccines; Zinc compounds; canine leishmaniasis; compassionate trial; immunotherapy; Leishmania; Lung Cancer; Mouse tumors; photo-inactivation; phthalocyanine; Singlet oxygen; vaccination; Vaccine carriers; Vaccine safety; Diseases
Publisher
SPIE
Type
conference paper