Photosensitizing antibody-fluorophore conjugates
Inventors
Kobayashi, Hisataka • Choyke, Peter • Mitsunaga, Makoto • Bernardo, Marcelino
Assignees
US Department of Health and Human Services
Publication Number
US-8524239-B2
Publication Date
2013-09-03
Expiration Date
2031-07-11
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Abstract
The present disclosure relates to compositions and methods of killing cells in vitro or in vivo. In particular examples, the method includes contacting a cell having a cell surface protein with a therapeutically effective amount of an antibody-IR700 molecule, wherein the antibody specifically binds to the cell surface protein. In particular examples the antibody recognizes a tumor-specific antigen on the surface of a tumor cell. The cell is subsequently irradiated, such as at a wavelength of 660 to 740 nm at a dose of at least 1 J cm−2, thereby killing the cell. Also provided are wearable devices that include an article of clothing, jewelry, or covering; and an NIR LED incorporated into the article, which can be used with the disclosed methods.
Core Innovation
The invention provides compositions and methods for killing target cells, such as tumor cells, using antibody-IR700 molecules that specifically bind to cell surface proteins. Following binding, the cells are irradiated with near-infrared (NIR) light at wavelengths from 660 to 740 nm, typically at doses of at least 1 J cm−2, to induce cell death. The antibody component targets tumor-specific antigens, such as HER1, HER2, or PSMA, enabling selective killing of cancer cells while sparing normal cells.
The problem addressed is the lack of effective therapies that selectively kill tumor cells without damaging non-cancerous cells, a limitation in conventional cancer treatments including surgery, radiation, and chemotherapy. Existing photodynamic therapies using non-targeted photosensitizers cause serious side effects due to uptake in normal tissues. There is a need for therapies combining high selectivity and minimal side effects.
The disclosed antibody-IR700 conjugates overcome these challenges by combining highly specific tumor-targeting antibodies with a photosensitizer activated only upon binding to cell membranes of target cells and subsequent NIR irradiation. This approach provides targeted phototoxicity primarily dependent on membrane binding rather than internalization or reactive oxygen species (ROS) production, improving selective tumor cell killing. Additionally, wearable devices incorporating near-infrared light emitting diodes (LEDs) are provided for extended treatments, allowing continuous irradiation of circulating tumor cells in vivo.
Claims Coverage
The patent includes one independent claim focused on a method for treating tumors using antibody-IR700 molecules and NIR irradiation. Key inventive features relate to the antibody conjugate, irradiation parameters, and applications.
Method of tumor treatment using antibody-IR700 conjugates and NIR irradiation
A method comprising administering a therapeutically effective amount of one or more antibody-IR700 molecules targeting a cell surface protein on a tumor, followed by irradiation at 660 to 740 nm at a dose of at least 1 J cm−2 to treat the tumor in the subject.
Use of tumor-specific antibodies conjugated to IR700
The antibody binds selectively to tumor-specific proteins such as HER1, HER2, CD20, CD25, CD33, CD52, or PSMA, enabling selective phototoxicity upon irradiation.
Irradiation at near-infrared wavelengths with specified doses
Irradiation of the tumor or tumor cells is conducted at wavelengths specifically between 660-740 nm, preferably around 680 nm, at doses sufficient to induce cell killing (at least 1 J cm−2).
Treatment of tumors in blood using wearable NIR LED devices
Irradiation of tumors or tumor cells circulating in blood using devices worn by the subject that incorporate near-infrared light emitting diodes (NIR LEDs), allowing continuous exposure and treatment.
Selection of subjects based on tumor antigen expression
Selecting subjects with tumors expressing a cell surface protein that specifically binds to the antibody-IR700 molecule prior to treatment.
Detection of tumors using sub-therapeutic doses of antibody-IR700 and light
Contacting tumors with less than therapeutically effective amounts of antibody-IR700 molecules and irradiating at low light doses to permit tumor detection by fluorescence without killing.
The claims collectively cover a method of selectively treating tumors with antibody-IR700 conjugates followed by near-infrared irradiation, specifying tumor antigen targets, irradiation parameters, subject selection, and wearable device-assisted treatment, as well as applications in tumor detection and increased survival.
Stated Advantages
Provides highly selective killing of tumor cells while minimizing damage to normal cells due to antibody-specific targeting.
Enables deep tissue penetration using near-infrared light for efficient phototoxicity.
Reduces off-target effects and side effects common in conventional photodynamic therapy by activation only upon antibody binding to tumor cells.
Allows for continuous, non-invasive treatment of circulating tumor cells via wearable NIR LED devices incorporated into clothing or accessories.
Incorporates diagnostic fluorescence enabling guidance of therapy and monitoring of treatment efficacy.
Permits repeated treatments without the cumulative toxicity associated with ionizing radiation.
Documented Applications
Treatment of solid tumors expressing tumor-specific antigens, including cancers of breast, liver, colon, ovary, prostate, pancreas, brain, cervix, bone, skin, lung, head and neck.
Treatment of blood cancers, including leukemias and lymphomas expressing target antigens.
Treatment of metastatic tumors located in various organs.
Therapy for circulating tumor cells in blood or lymph using wearable devices incorporating NIR LEDs.
Tumor visualization and margin detection during surgical or endoscopic procedures via lower dose antibody-IR700 and NIR irradiation.
Potential treatment for transplant rejection targeting CD25 expressing cells.
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