Photosensitizing antibody-fluorophore conjugates
Inventors
Kobayashi, Hisataka • Choyke, Peter
Assignees
US Department of Health and Human Services
Publication Number
US-12296013-B2
Publication Date
2025-05-13
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 antibody-IR700 molecules and methods to kill target cells, such as tumor cells, by specifically binding to cell surface proteins and subsequent irradiation with near infrared (NIR) light. The antibodies recognize tumor-specific antigens on tumor cell surfaces, and the irradiation occurs at a wavelength of about 660 to 740 nm, with doses of at least 1 J cm−2, causing selective cell death. The antibody-IR700 conjugates target cells in vitro and in vivo, sparing non-target or normal cells from significant killing.
The approach overcomes the limitations of conventional cancer therapies which do not effectively distinguish tumor cells from normal cells, often causing collateral damage. Traditional photodynamic therapy (PDT) is limited by non-target photosensitizer uptake in normal tissues. This invention solves the problem of off-target toxicity by using antibody conjugates that are only activated upon binding to specific cell surface proteins, thus minimizing side effects and improving killing selectivity.
The disclosure also includes wearable or portable devices integrating NIR light emitting diodes (LEDs), incorporated into everyday items such as clothing or jewelry. These devices enable continuous or extended NIR irradiation targeting cells circulating in the blood or lymph, facilitating treatment of metastases or circulating tumor cells with minimal interference in patient lifestyle. The fluorescence emitted from these conjugates enables both guidance of therapy and monitoring of therapeutic effects.
Claims Coverage
The patent includes two independent claims covering compositions and combination therapies involving antibody-IR700 conjugates targeting PSMA with J591 antibodies and fragments thereof.
Phototoxic conjugate comprising IR700 conjugated to anti-PSMA antibody J591
A pharmaceutical composition including a phototoxic conjugate formed by conjugating IR700 to an antibody specific to prostate-specific membrane antigen (PSMA), specifically the antibody J591 or its antigen binding fragments, combined with a pharmaceutically acceptable carrier.
Combination therapy including antibody-IR700 conjugate and additional therapeutic agent
A combination composition comprising a phototoxic conjugate as above with IR700-J591 antibody conjugate and a separate pharmaceutical composition containing an additional therapeutic agent such as anti-cancer or anti-neoplastic agents including chemotherapeutics, radiotherapeutics, kinase inhibitors, or immunomodulators.
The independent claims focus on pharmaceutical compositions and combination therapies involving antibody-IR700 conjugates specifically using anti-PSMA antibody J591 and its fragments conjugated to IR700, alone or combined with other therapeutic agents to achieve targeted phototoxic effects.
Stated Advantages
Selective killing of tumor cells expressing target antigens with minimal harm to normal cells.
Use of NIR light allows deeper tissue penetration facilitating effective in vivo treatment.
Fluorescence emitted by conjugates enables real-time monitoring and guidance of therapy.
Wearable NIR LED devices permit prolonged and non-invasive treatment of circulating tumor cells.
Reduced off-target phototoxicity compared to conventional photosensitizers due to antibody-specific targeting.
Compatibility with multiple cancer types expressing different tumor-specific antigens through antibody selection.
Documented Applications
Killing tumor cells in vitro and in vivo by targeted photoimmunotherapy using antibody-IR700 conjugates.
Treatment of solid tumors and liquid tumors such as leukemias and lymphomas expressing specific tumor antigens.
Use of wearable NIR LED devices in patients to treat circulating tumor cells or metastases in blood or lymphatic systems.
Combination cancer therapies incorporating antibody-IR700 conjugates with chemotherapeutics, radiotherapy, or immunomodulators.
Monitoring of tumor location, margins, and treatment efficacy during surgical procedures using antibody-IR700 fluorescence.
Treatment of transplant rejection by targeting specific cell surface proteins such as CD25 with antibody-IR700 conjugates.
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