When it comes to cancer treatment, one must be able to outsmart th disease. Combining the light-based approach called photodynamic therapy with immunotherapy has emerged as one of the most powerful ways to do this, because the combinatino bypasses or overrides many of the mechanisms that cancer uses to persist in the body.
One of the immunotherapy strategies that’s being investigated is known as oncolytic viral therapy. This novel cancer treatment involves the use of viruses that selectively kill cancer cells and stimulate an immune response against tumors. The oncolytic virus replicates inside cancer cells, eventually causing them to burst and die. The dying cells release new viruses, as well as a variety of tumor-specific antigens (proteins unique to the tumor) that can stimulate an immune response against malignant cells throughout the body.
Although the virus can enter cancer cells and normal cells alike, normal cells have the built-in means to destroy the virus; cancer cells do not. This makes oncolytic viral therapy an especially attractive treatment because, in principle, it can destroy even those cancer cells that are resistant to chemotherapy and radiotherapy. Recent evidence suggests that oncolytic viral therapy can be effective against a wide range of human cancers, with the potential to reach not only the primary tumor but also distant metastases.
Scientists from the St James’s University Hospital, in Leeds, United Kingdom recently attempted to combine oncolytic viral therapy with PDT in order to destroy pancreatic cancer. This cancer is usually diagnosed at a late stage and is notoriously resistant to conventional chemotherapy and radiotherpay. The great majority of pancreatic cancer patients will die within two years of their diagnosis.
“Oncolytic viral therapy and photodynamic therapy are potential therapies for inoperable or advanced pancreatic cancer,” the researchers write in the 26 February 2015 issue of the British medical journal, the Lancet. “Our aim was to investigate the anti-cancer killing effects of reovirus therapy combined with protoporphyrin IX (PpIX)-mediated photodynamic therapy on a variety of human pancreatic cancer cell lines.”
In this laboratory study, two different pancreatic cancer cell lines and a non-cancer cell line (the control group) were infected with the oncolytic virus for 48 hours. In addition, the cells were incubated with a photosensitizer for four hours, before being exposed to red light-emitting diodes at a wavelength of 653 nm. The killing effects of viral therapy combined with PDT were analyzed.
The oncolytic virus therapy triggered cell death in about half of the two pancreatic lines (57%), while PDT caused cell death in a dose-dependent manner). Combining the two treatments led to a significantly increased killing effect compared to either treatment alone—an impressive 100% cell death in the two pancreatic cell lines. There was no difference in the killing effect if the virus was given before or after PDT.
“To our knowledge, this is the first [cell culture] study to combine reovirus oncolytic viral therapy with PpIX-mediated photodynamic therapy to treat pancreatic cancer,” the authors write. “These results show a significant additive effect in cell killing and they provide initial evidence for a novel combined therapeutic intervention.”
Khaled YS, Wright K, Melcher A, Jayne D. Anti-cancer effects of oncolytic viral therapy combined with photodynamic therapy in human pancreatic cancer cell lines. Lancet. 2015 Feb 26;385 Suppl 1:S56. doi: 10.1016/S0140-6736(15)60371-3.
Zheng Y, Yin G, Le V, Zhang A, Chen S, Liang X, Liu J. Photodynamic-therapy Activates Immune Response by disrupting Immunity Homeostasis of Tumor Cells, which Generates Vaccine for Cancer Therapy. Int J Biol Sci. 2016 Jan 1;12(1):120-32.
Kleinovink JW, van Driel PB, Snoeks TJ, Prokopi N, Fransen MF, Cruz LJ, Mezzanotte L, Chan A, Löwik CW, Ossendorp F. Combination of Photodynamic Therapy and Specific Immunotherapy Efficiently Eradicates Established Tumors. Clin Cancer Res. 2015 Nov 6. [Epub ahead of print]