Photoimmunotherapy ( PIT ), also referred to as photothermal phototherapy and photothermalimmunology , is an oncology treatment that combines photodynamic tumor therapy with immunotherapy treatment. Combining photodynamic therapy with immunotherapy improves immunostimulation response and has a synergistic effect for the treatment of metastatic cancer.
PIT is a type of molecular targeted cancer therapy, which enables selective cancer cell destruction without damaging normal tissue. It is a light-based cancer therapy, developed by Professor Kobayashi and colleagues at the National Cancer Institute, Bethesda, Maryland.
Conventional photodynamic therapy (PDT) uses non-specific photosensitizers that can be activated by non-ionizing light to kill cancer cells. Photosensitizers are molecules that rapidly destroy cells despite the production of reactive oxygen species (ROS) when exposed to light at certain wavelengths. However, this PDT treatment produces serious side effects because unexpected photosensitizers are also taken by normal tissue.
PIT treatment avoids the problem of side-effects through the creation of targeted photosensitizers, involving two components: monoclonal antibodies (mAbs) that recognize specific proteins on the surface of cancer cells, and unexpected photosensitizers. Although new mAb-based photosensitizers are distributed throughout the body, it can be activated by light for targeted PIT only when bound to a specific protein in the cancer cell membrane.
The research team at Professor Kobayashi's lab combines anti-tumor antibodies that target the human epidermal growth factor receptor to phthalocyanine dye, IRDye 700DX, which is activated by near infrared light. IRDye 700DX was chosen because of strong hydrophilicity and cytotoxicity induced in association with the cell membrane and subsequent activation. Various cancers, such as breast and pancreatic cancers, express epidermal growth factor receptors. This new photosensitizing compound utilizes the IRDye 700DX NHS Ester referred to as "mAb-IR700 conjugates".
In-vitro studies have shown that mAb-IR700 kills tumor cells a few seconds after near-infrared light radiation. There is also a positive correlation between the intensity of excitation light and the percentage of cell death. Infrared alone or mAb-IR700 conjugation alone does not cause damage to normal cells. When the xenografted-tumor mice were treated with mAb-IR700 and near-infrared light, significant tumor shrinkage was observed. By conjugating fractionation mAB-IR700 followed by irradiated NIR light repeated systematically to tumors, 80 percent of tumor cells have been eradicated and the survival of mice is significantly prolonged. Based on the current hypothesis, cell death caused by PIT is caused by the rapid expansion of local water on the formation of holes in the membrane.
Another desirable feature of PIT using the mAb-IR700 conjugate is that it also emits fluorescence light after activation. Therefore prior to PIT, mAb-IR700 may be administered at lower doses to guide excitation light applications to tumor tissue, further minimizing unnecessary exposure to the surrounding tissue.
PIT is a highly selective and clinically feasible method of therapy for treatment of mAb binding tumors with minimal off-target effects. For future directions, researchers try to conjugate other monoclonal antibodies to phthalocyanine, creating a highly flexible therapeutic platform.
Video Photoimmunotherapy
See also
- Combinatorial and combinations of immunotherapy
- Cryoimmunotherapy
Maps Photoimmunotherapy
References
Bibliography
- Kobayashi, Hisataka. "Illuminate the potential of targeting near-infrared phototherapy cancer."
- Sato, Kazuhide, et al. "Photo immunotherapy: the comparative effectiveness of two monoclonal antibodies targeting epidermal growth factor receptors." Molecular oncology 8.3 (2014): 620-632.
External links
- Technical information about IRDye 700DX NIR Dye
- Hisataka Kobayashi, M.D., Ph.D.
Source of the article : Wikipedia
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