National Institutes of Health, a Component of the US Dept. of Health & Human Services

Shimadzu Corporation

The United States of America, Represented by the S

Hisataka Kobayashi

Peter Choyke

Martin John Schnermann

Marcelino Bernardo

Martin Wade Brechbiel

Roger Rauhauser Nani

Robert A Star

Noriko Sato

Alexander Patrick Gorka

Kazuhide Sato

Makoto Mitsunaga

Masayuki Nishimura

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, 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.

Photosensitizing antibody-fluorophore conjugates

A method and treatment for testing efficiency and effectiveness of a near infrared photoimmunotherapy treatment includes injecting an antibody photosensitizer conjugate (APC) into a patient, applying radiation to the patient, thereby causing the APC to release a ligand, which is excreted in the patient's urine, detecting the presence of the ligand with liquid chromatography-mass spectrometry, measuring and quantifying an amount of the ligand present in the patient's urine based on analytical results of the liquid chromatography-mass spectrometry, and determining the effectiveness of the near infrared photo-immunotherapy treatment based on the measured quantified amount of the ligand present in the patient's urine so as to determine an amount of APC remaining in the patient.

Method and apparatus for testing near infrared-photoimmunotherapy treatment

This disclosure provides IR700-molecule conjugates and methods of their use to remove (e.g., separate or isolate) a target from a sample in vivo or from a subject in vitro. It is shown herein that exposure of IR700 to near infrared (NIR) light removes a portion of IR700, changing it from a hydrophilic molecule, to one that is hydrophobic, resulting in aggregation of IR700 and anything bound to it. For example, the disclosed IR700-molecule conjugates and methods provide photo-controlled ways to control the pharmacokinetics of a drug in vivo, and can be used to remove undesired agents from environmental or food samples or to isolate target molecules in a laboratory.

Photo-controlled removal of targets in vitro and in vivo

The present disclosure relates to compositions and methods of killing cells. 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, such as 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. The cell is also contacted with one or more therapeutic agents (such as an anti-cancer agent), for example about 0 to 8 hours after irradiating the cell, thereby killing the cell. Also provided are methods of imaging cell killing in real time, using fluorescence lifetime imaging. 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.

It is shown that CD25-targeted near-infrared photo-immunotherapy causes a unique, rapid and spatially selective depletion of Tregs leading to regression of the treated tumor and inducing systemic immunologic responses in untreated tumors. Based on these observations, provided are compositions and methods of killing immune suppressor cells, for example to treat cancer. Reducing the number of suppressor cells in a subject can remove suppression of effector T cells, for example, to treat cancer using the subject's own immune system. In particular examples, the method includes contacting suppressor cells having a suppressor cell surface protein with an antibody-IR700 molecule, wherein the antibody specifically binds to the suppressor cell surface protein, and in some examples the antibody does not have a functional Fc region. The cell is subsequently irradiated, such as at a wavelength of 660 to 740 nm, for example at a dose of at least 4 J cm.

Near infrared photoimmunotherapy (NIR-PIT) of suppressor cells to treat cancer

Embodiments of near-infrared light-cleavable heptamethine cyanine-based conjugates, particularly targeting agent-drug conjugates, according to Formula I and conjugate precursors are disclosed. The disclosed targeting agent-drug conjugates are useful for targeted delivery and release of a drug. Methods of making and using the conjugates and precursors also are disclosed. 

Near-IR light-cleavable conjugates and conjugate precursors

Small dendrimer-based MRI contrast agents are disclosed to accumulate in renal tubules. The accumulation enables visualization of renal structure and function, permitting assessment of structural and functional damage to the kidneys. In a disclosed embodiment, six, small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole body retention, and renal MRI images were evaluated in mice. Surprisingly, despite having unequal renal clearance properties, all of the dendrimer agents clearly visualized the renal anatomy and proximal straight tubules of the mice better than Gd-[DTPA]-dimeglumine. Dendrimer conjugate contrast agents prepared from PAMAM-G2D, DAB-G3D, and DAB-G2D dendrimers were excreted rapidly and may be acceptable for use in clinical applications.

Growing community of inventors

Laurel, MD, United States of America

Hisataka Kobayashi