Photoimmunotherapy

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Photoimmunotherapy
Specialty oncology

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. [1] [2] [3]

Contents

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. [4] 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.

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 ] are molecules that rapidly destroy cells though the production of reactive oxygen species (ROS) when exposed to light at specific wavelength. [5] However, this PDT treatment results in serious side effects because non-targeted photosensitizers are also taken up by normal tissues.

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. [6]

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, [7] 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. [6] A variety of cancers, such as breast and pancreatic cancers over-express epidermal growth factor receptors. [8] 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. [9] 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.

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.

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.

See also

Related Research Articles

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<span class="mw-page-title-main">Photosensitizer</span> Type of molecule reacting to light

Photosensitizers are light absorbers that alter the course of a photochemical reaction. They usually are catalysts. They can function by many mechanisms, sometimes they donate an electron to the substrate, sometimes they abstract a hydrogen atom from the substrate. At the end of this process, the photosensitizer returns to its ground state, where it remains chemically intact, poised to absorb more light. One branch of chemistry which frequently utilizes photosensitizers is polymer chemistry, using photosensitizers in reactions such as photopolymerization, photocrosslinking, and photodegradation. Photosensitizers are also used to generate prolonged excited electronic states in organic molecules with uses in photocatalysis, photon upconversion and photodynamic therapy. Generally, photosensitizers absorb electromagnetic radiation consisting of infrared radiation, visible light radiation, and ultraviolet radiation and transfer absorbed energy into neighboring molecules. This absorption of light is made possible by photosensitizers' large de-localized π-systems, which lowers the energy of HOMO and LUMO orbitals to promote photoexcitation. While many photosensitizers are organic or organometallic compounds, there are also examples of using semiconductor quantum dots as photosensitizers.

<span class="mw-page-title-main">Targeted therapy</span> Type of therapy

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<span class="mw-page-title-main">Monoclonal antibody therapy</span> Form of immunotherapy

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<span class="mw-page-title-main">Trifunctional antibody</span> Monoclonal antibody

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<span class="mw-page-title-main">Sonodynamic therapy</span>

Sonodynamic therapy (SDT) is a noninvasive treatment, often used for tumor irradiation, that utilizes a sonosensitizer and the deep penetration of ultrasound to treat lesions of varying depths by reducing target cell number and preventing future tumor growth. Many existing cancer treatment strategies cause systemic toxicity or cannot penetrate tissue deep enough to reach the entire tumor; however, emerging ultrasound stimulated therapies could offer an alternative to these treatments with their increased efficiency, greater penetration depth, and reduced side effects. Sonodynamic therapy could be used to treat cancers and other diseases, such as atherosclerosis, and diminish the risk associated with other treatment strategies since it induces cytotoxic effects only when externally stimulated by ultrasound and only at the cancerous region, as opposed to the systemic administration of chemotherapy drugs.

<span class="mw-page-title-main">Gold nanoparticles in chemotherapy</span> Drug delivery technique using gold nanoparticles as vectors

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Photodynamic/photothermal combination therapy involves the usage of a chemical compound or nanomaterial that, when irradiated at a certain wavelength, converts light energy into reactive oxygen species (ROS) and heat. This has shown to be highly effective in the treatment of skin infections, showing increased wound healing rates and a lower impact on human cell viability than photodynamic (PD) or photothermal (PT) therapies. The compounds involved often employ additional mechanisms of action or side effect reduction mechanisms, further increasing their efficacy.

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References

  1. ↑ Wang C, Xu L, Liang C, Xiang J, Peng R, Liu Z (2014). "Immunological responses triggered by photothermal therapy with carbon nanotubes in combination with anti-CTLA-4 therapy to inhibit cancer metastasis". Adv Mater. 26 (48): 8154–62. Bibcode:2014AdM....26.8154W. doi:10.1002/adma.201402996. PMID   25331930. S2CID   5421261.
  2. ↑ Lin, Z; et al. (2015). "Photothermal ablation of bone metastasis of breast cancer using PEGylated multi-walled carbon nanotubes". Sci Rep. 5: 11709. Bibcode:2015NatSR...511709L. doi:10.1038/srep11709. PMC   4485034 . PMID   26122018.
  3. ↑ Chen, Q; et al. (2016). "Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy". Nat Commun. 7: 13193. Bibcode:2016NatCo...713193C. doi:10.1038/ncomms13193. PMC   5078754 . PMID   27767031.
  4. ↑ Mew, Daphne; Chi-Kit Wat; G. H. Neil Towers; Julia Levy (March 1983). "Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates". The Journal of Immunology. 130 (3): 1473–1477. doi: 10.4049/jimmunol.130.3.1473 . PMID   6185591. S2CID   7320471.
  5. ↑ Park, S (May 2007). "Delivery of photosensitizers for photodynamic therapy". Korean J Gastroenterol. 49 (5): 300–313. PMID   17525518.
  6. 1 2 Mitsunaga, M; Ogawa, M; Kosaka, N; Rosenblum, L. T; Choyke, P. L; Kobayashi, H (2011). "Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules". Nature Medicine. 17 (12): 1685–1691. doi:10.1038/nm.2554. PMC   3233641 . PMID   22057348.
  7. ↑ Peng, Xinzhan; Daniel R. Draney; William M. Volcheck; Gregory R. Bashford; Donald T. Lamb; Daniel L. Grone; Yonghong Zhang; Craig M. Johnson (14 February 2006). Achilefu, Samuel; Bornhop, Darryl J; Raghavachari, Ramesh (eds.). "Phthalocyanine dye as an extremely photostable and highly fluorescent near-infrared labeling reagent". Proc. SPIE 6097, Optical Molecular Probes for Biomedical Applications, 60970E. Optical Molecular Probes for Biomedical Applications. 6097: 60970E. Bibcode:2006SPIE.6097..113P. doi:10.1117/12.669173. S2CID   98409379.
  8. ↑ 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.
  9. ↑ 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

Bibliography

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