NIR-conjugated tumor-specific antibodies and uses thereof
Inventors
YAZAKI, Paul • SHIVELY, Jack • BOUVET, Michael • DeLong, Jonathan • Fong, Yuman
Assignees
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Publication Number
US-12178887-B2
Publication Date
2024-12-31
Expiration Date
Abstract
Disclosed is a tumor-specific antibody and fluorophore conjugate for detecting, localizing and imaging of various tumors. Also disclosed are methods for detecting, localizing and imaging a solid tumor before or during a tumor resection surgery using the antibody-fluorophore conjugate.
Core Innovation
The invention relates to antibody-fluorophore conjugates for tumor-specific near-infrared (NIR) fluorescence detection and localization. It describes humanized antibodies targeting solid tumors expressing CEA and/or TAG-72, including tumor-specific labeling using NIR fluorophores. The conjugates are used for preoperative and intraoperative detection and localization and fluorescence-guided surgical resection, with an emphasis on NIR imaging performance.
The core concept includes conjugating a tumor-specific antibody to NIR fluorophores and using the resulting fluorescence for imaging. The description includes examples using humanized anti-CEA M5A and humanized anti-TAG-72 CC49 antibodies, and NIR fluorophores including Li-Cor IRDye800CW-NHS and Intuitive IR800. It further discusses that improved contrast and tumor-to-background signal are achieved with NIR fluorophore labeling.
The invention also encompasses optional radioactive labeling in addition to NIR fluorescence. It describes dual-fluorescence/radioimaging concepts and radioactive labeling with isotopes such as 64Cu and 125I, including attachment using chelation with a chelating agent notably DOTA. The disclosed imaging behavior includes tumor imaging timing and reported tumor-to-background ratio performance.
Claims Coverage
The independent claim covers an antibody-fluorophore conjugate with one main inventive concept: a tumor-specific PEG-modified NIR fluorophore conjugate using an anti-TAG-72 antibody. Dependent claims further narrow the antibody to humanized and then CC49 and optionally add radioactive isotope labeling via a chelating agent, with DOTA identified as the chelator.
PEG modified NIR fluorophore conjugate with tumor-specific anti-TAG-72 antibody
An antibody-fluorophore conjugate comprising a tumor-specific antibody conjugated to a PEG modified NIR fluorophore, wherein the antibody is an anti-TAG-72 antibody.
Humanized anti-TAG-72 antibody conjugate
The conjugate wherein the antibody is a humanized anti-TAG-72 antibody.
Humanized anti-TAG-72 CC49 antibody conjugate
The conjugate wherein the antibody is a humanized anti-TAG-72 CC49 antibody.
Radioactive isotope labeled antibody conjugate
The conjugate wherein the antibody is labeled with a radioactive isotope.
Chelated attachment of radioactive isotope to antibody
The conjugate wherein a radioactive isotope is attached to the antibody via a chelating agent.
DOTA chelating agent for radioactive isotope attachment
The conjugate wherein the chelating agent is DOTA.
Across the claim set provided, coverage centers on an antibody-fluorophore conjugate using a tumor-specific PEG modified NIR fluorophore conjugated to an anti-TAG-72 antibody, narrowed to humanized forms and specifically humanized CC49. Optional embodiments add radioactive isotope labeling, where the isotope is attached through a chelating agent, specifically DOTA.
Stated Advantages
Improved contrast and tumor-to-background signal for NIR imaging (as stated in the provided summary content).
Improved penetration and contrast with NIR fluorophores (as stated in the provided summary content).
Documented Applications
Preoperative and intraoperative detection/localization of CEA- and/or TAG-72-expressing solid tumors using tumor-specific NIR fluorescence.
Fluorescence-guided surgical resection using the disclosed NIR antibody-fluorophore conjugates.
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