{{Infobox medical intervention | name = Photoimmunotherapy | synonym = | image = | caption = | alt = | pronounce = | specialty = oncology | synonyms = | ICD10 = | ICD9 = | ICD9unlinked = | CPT = | MeshID = | LOINC = | other_codes = | MedlinePlus = | eMedicine = }} '''Photoimmunotherapy''' ('''PIT''') is an oncological treatment that combines photodynamic therapy of tumor with immunotherapy treatment. Combining photodynamic therapy with immunotherapy enhances the immunostimulating response and has synergistic effects for metastatic cancer treatment.<ref>{{Cite journal | title = Immunological responses triggered by photothermal therapy with carbon nanotubes in combination with anti-CTLA-4 therapy to inhibit cancer metastasis.| year = 2014| doi = 10.1002/adma.201402996| pmid=25331930| volume=26| issue = 48| journal=Adv Mater| pages=8154–62| vauthors=Wang C, Xu L, Liang C, Xiang J, Peng R, Liu Z| bibcode = 2014AdM....26.8154W| s2cid = 5421261}}</ref><ref>{{Cite journal | author = Lin, Z |display-authors=et al | title = Photothermal ablation of bone metastasis of breast cancer using PEGylated multi-walled carbon nanotubes.| year = 2015| pmid = 26122018| doi = 10.1038/srep11709| pmc=4485034| volume=5| journal=Sci Rep| article-number=11709|bibcode=2015NatSR...511709L }}</ref><ref>{{Cite journal | author = Chen, Q |display-authors=et al | title = Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy.| year = 2016| pmid = 27767031| doi = 10.1038/ncomms13193| pmc=5078754| volume=7| journal=Nat Commun| article-number=13193|bibcode=2016NatCo...713193C }}</ref>
PIT is type of molecular targeted cancer therapy, which allows the selective destruction of cancer cells without any damage to normal tissues. It is a light-based cancer therapy, which was developed and pioneered by Professor Julia Levy and colleagues at the University of British Columbia, Canada, in 1983. <ref>{{cite journal|last=Mew|first=Daphne|author2=Chi-Kit Wat |author3=G. H. Neil Towers |author4=Julia Levy |title=Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates |journal=The Journal of Immunology |date=March 1983 |volume=130 |issue=3 |pages=1473–1477 |doi=10.4049/jimmunol.130.3.1473 |pmid=6185591|s2cid=7320471 |url=http://www.jimmunol.org/content/130/3/1473.short |doi-access=free |url-access=subscription }}</ref> Professor Julia Levy's research has also been pivotal in the clinical approval of Visudyne and Photofrin. Over the last 35 years, PIT has been studied extensively in vitro and in vivo by numerous research teams all over the world. More recently, significant strides in PIT have been made by Professor Kobayashi and his colleagues at National Cancer Institute, Bethesda, Maryland.{{cn|date=April 2025}}
Conventional photodynamic therapy (PDT) uses a non-specific photosensitizer which can be activated by a non-ionizing light to kill cancer cells. Photosensitizers{{Broken anchor|date=2024-07-01|bot=User:Cewbot/log/20201008/configuration|target_link=Photosensitizer#Photosensitization|reason= }} are molecules that rapidly destroy cells though the production of reactive oxygen species (ROS) when exposed to light at specific wavelength.<ref>{{cite journal |vauthors=Park, S |date=May 2007 |title=Delivery of photosensitizers for photodynamic therapy |journal=Korean J Gastroenterol |volume=49 |issue=5 |pages=300–313|pmid=17525518 }}</ref> However, this PDT treatment results in serious side effects because non-targeted photosensitizers are also taken up by normal tissues.{{cn|date=April 2025}}
PIT treatment avoids the side effects problem through the creation of a targeted-photosensitizer, which involves two components: a monoclonal antibody (mAb) which recognizes specific proteins on the surface of cancer cells, and a non-targeted photosensitizer. Even though the new mAb-based photosensitizers are distributed throughout the body, it can be activated by light for targeted PIT only when bound to specific proteins on cancer cellular membrane.<ref name="Mitsunaga">{{cite journal|author=Mitsunaga, M|author2=Ogawa, M |author3=Kosaka, N |author4=Rosenblum, L. T |author5=Choyke, P. L |author6=Kobayashi, H |title=Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules |journal=Nature Medicine|date=2011|volume=17 |issue=12 |doi=10.1038/nm.2554|pmc=3233641 |pages=1685–1691 |pmid=22057348}}</ref>
PIT has been previously published using a vast number of photosensitizers, such as porphyrins, chlorins and phthalocyanine dyes. The research team at Professor Kobayashi's lab coupled anti-tumor antibodies targeting human epidermal growth factor receptors to a water soluble phthalocyanine dye, IRDye 700DX,<ref>{{cite journal|last=Peng|first=Xinzhan|author2=Daniel R. Draney |author3=William M. Volcheck |author4=Gregory R. Bashford |author5=Donald T. Lamb |author6=Daniel L. Grone |author7=Yonghong Zhang |author8=Craig M. Johnson |editor1-first=Samuel|editor1-last=Achilefu|editor2-first=Darryl J|editor2-last=Bornhop|editor3-first=Ramesh|editor3-last=Raghavachari|title=Phthalocyanine dye as an extremely photostable and highly fluorescent near-infrared labeling reagent|journal=Proc. SPIE 6097, Optical Molecular Probes for Biomedical Applications, 60970E|date=14 February 2006|volume=6097|pages=60970E|doi=10.1117/12.669173|series=Optical Molecular Probes for Biomedical Applications|bibcode=2006SPIE.6097..113P|s2cid=98409379}}</ref> which is activated by near-infrared light. IRDye 700DX was chosen for its hydrophilicity and strong cytotoxicity induced upon association with the cellular membrane and subsequent activation.<ref name="Mitsunaga" /> A variety of cancers, such as breast and pancreatic cancers over-express epidermal growth factor receptors.<ref>McKeage K, Perry CM., Trastuzumab: a review of its use in the treatment of metastatic breast cancer overexpressing HER2., Drugs. 2002;62(1):209-43.</ref> This new photosensitizing compound utilizing IRDye 700DX NHS Ester was referred to as "mAb-IR700 conjugates".
In Vitro studies showed that mAb-IR700 killed tumor cells seconds after the near-infrared light irradiation. There was also a positive correlation between the intensity of excitation light and percentage of cell death. Infrared light alone or mAb-IR700 conjugate alone did not cause any damage to normal cells. When tumor-xenografted mice were treated with mAb-IR700 and near-infrared light, significant tumor shrinkage was observed. With fractionated administration of mAB–IR700 conjugate followed by systematic repeated NIR light irradiation to the tumor, 80 percent of tumor cells were eradicated and the mice's survival were significantly prolonged.<ref>Makoto Mitsunaga, Takahito Nakajima, Kohei Sano, Peter L. Choyke, and Hisataka Kobayashi, (2012) Near-infrared Theranostic Photoimmunotherapy (PIT): Repeated Exposure of Light Enhances the Effect of Immunoconjugate, Bioconjugate Chem., 2012, 23 (3), 604–609</ref> Based on the current hypothesis, cell death induced by PIT was caused by rapid expansion of local water upon the formation of holes in the membrane.{{cn|date=April 2025}}
Another desirable feature of PIT using mAb-IR700 conjugate is that it also emits fluorescence light upon activation. Therefore before PIT, mAb-IR700 can be administered at a lower dosage to guide the application of excitation light to tumor tissues, further minimizing unnecessary light exposure to surrounding tissues.{{cn|date=April 2025}}
PIT is a promising highly selective and clinically feasible therapeutic method for treatment of mAb-binding tumors with minimal off-target effects. For future directions, researchers are trying to conjugate a variety of other monoclonal antibodies to phthalocyanine, creating a highly flexible therapeutic platform.{{cn|date=April 2025}} __NOTOC__ == See also == * Combinatorial ablation and immunotherapy * Cryoimmunotherapy
== References == {{Reflist}}
== Bibliography == * Kobayashi, Hisataka. "[http://www.biochemist.org/bio/03806/0016/038060016.pdf Illuminating the cancer-targeting potential of near-infrared photoimmunotherapy.]" * {{cite journal |author=Sato, Kazuhide |display-authors=et al |title=Photoimmunotherapy: comparative effectiveness of two monoclonal antibodies targeting the epidermal growth factor receptor |journal=Molecular Oncology |volume=8 |issue=3 |date=May 2014 |pages=620–632 |pmid=24508062 |pmc=4004687 |doi=10.1016/j.molonc.2014.01.006 }}
== External links == * [http://www.licor.com/clinical_translation/irdye_700DX_background.html Technical information on IRDye 700DX NIR Dye] * [https://ccr.cancer.gov/Molecular-Imaging-Program/hisataka-kobayashi Hisataka Kobayashi, M.D., Ph.D.]
Category:Light therapy Category:Immunotherapy