Application of anti-CD39L3 antibodies for use in disease diagnostics and imaging
Inventors
Powers, Alvin C. • Brissova, Marcela • DAI, Chunhua • Phillips, Neil • SAUNDERS, Diane
Assignees
US Department of Veterans Affairs • Vanderbilt University
Publication Number
US-11287427-B2
Publication Date
2022-03-29
Expiration Date
2038-06-11
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Abstract
In spite of significant efforts to identify β-cell-specific markers for β-cell imaging and purification, progress has been limited. Herein is disclosed a novel biomarker of human pancreatic β-cells, CD39L3 (also known as ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3)). Disclosed are compositions and methods for purifying and imaging β-cell using anti-CD39L3 antibodies.
Core Innovation
The invention discloses a novel biomarker of human pancreatic β-cells, CD39L3, also known as ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3). It presents compositions and methods for purifying and imaging β-cells using anti-CD39L3 antibodies. These methods enable detection through administration of anti-CD39L3 antibodies, nucleic acid probes specific for CD39, or labeled small molecules targeting CD39, followed by assays for the presence of these markers, either non-invasively with imaging techniques or invasively through tissue sampling.
The problem addressed is the lack of effective, specific, and non-invasive methods for identifying and quantifying pancreatic β-cell mass in subjects. Diabetes, both type 1 and type 2, involves dysfunction or destruction of insulin-secreting β-cells, but currently, β-cell mass cannot be non-invasively quantified in humans. Existing approaches like insulin secretion tests provide indirect and insufficient information. Surgical methods can quantify β-cell mass but are invasive and impractical for clinical use. Thus, there is a need for new targets and methods for detecting islet β-cells in vivo and ex vivo to aid diagnostics, understanding disease progression, and therapeutic evaluation.
The disclosed innovation solves this by identifying CD39L3 as a specific cell surface marker on human pancreatic β-cells, preserved in diabetic states, enabling separation of β-cells with high purity. Anti-CD39L3 antibodies can be used in methods of detecting β-cell mass non-invasively via imaging modalities such as bioluminescence imaging (BLI), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), computed tomography (CT), and fluorescence molecular tomography (FMT). Furthermore, these antibodies enable isolation of β-cells ex vivo using fluorescence activated cell sorting (FACS) or magnetic bead separation. Applications include detecting β-cell mass decline indicative of diabetes, testing therapeutic agents to increase β-cell mass, and isolating β-cells for transplantation therapy.
Claims Coverage
The patent contains multiple independent claims covering methods of detecting, isolating, and treating diabetes by targeting CD39L3 expressed on islet β-cells using anti-CD39L3 antibodies or related probes. The inventive features focus on the use of fluorescent labeling, magnetic beads conjugation, ex vivo and in vivo detection methods, isolation techniques, and transplantation of isolated β-cells.
Use of fluorescently labeled or magnetic bead-conjugated anti-CD39L3 antibodies to identify islet β-cells
This feature includes contacting pancreatic tissue with fluorescently labeled anti-CD39L3 antibodies or magnetic beads conjugated to anti-CD39L3 antibodies that specifically bind CD39L3 expressed on islet β-cells.
Assaying islet β-cell-bound anti-CD39L3 antibody to detect diabetes via decreased β-cell mass
This involves measuring the amount of islet β-cell-bound anti-CD39L3 antibody relative to a nondiabetic control, where a decrease indicates reduced β-cell mass and diabetes diagnosis.
Isolating CD39L3 expressing islet β-cells using magnetic beads or fluorescence activated cell sorting (FACS)
This inventive feature comprises isolating β-cells from donor pancreatic tissue after contacting with labeled anti-CD39L3 antibody by applying magnetic bead separation or FACS methods.
Transferring isolated CD39L3 expressing islet β-cells to treat diabetes in recipient subjects
This comprises transplanting isolated β-cells expressing CD39L3 into diabetic subjects to treat diabetes.
Ex vivo contacting of recipient pancreatic tissue with anti-CD39L3 antibody for β-cell mass assay
The method includes ex vivo application of the anti-CD39L3 antibody to recipient pancreatic tissue samples and assaying the β-cell-bound antibodies to detect β-cell mass.
In vivo contacting of pancreatic tissue with anti-CD39L3 antibody with detection via multiple imaging modalities
This feature involves in vivo contacting of pancreatic tissue with anti-CD39L3 antibody and detecting bound antibodies using imaging modalities including BLI, MRI, PET, SPECT, CT, and FMT.
The claims collectively cover innovative methods for diagnosing and treating diabetes by employing anti-CD39L3 antibodies or related probes to specifically identify, isolate, and quantify islet β-cells both in vivo and ex vivo, with applications to β-cell mass assessment, diabetes detection, and β-cell transplantation therapy.
Stated Advantages
Allows for non-invasive detection of islet β-cell mass, reducing the need for surgery or invasive procedures.
Provides a specific marker (CD39L3) for highly pure isolation of human β-cells.
Enables accurate assessment of β-cell mass and diabetes progression, improving early diagnostics and therapeutic evaluation.
Facilitates monitoring of islet transplantation success and the efficacy of agents designed to increase β-cell mass.
Documented Applications
Non-invasive detection of islet β-cell mass in subjects using anti-CD39L3 antibodies and imaging techniques.
Ex vivo isolation and purification of human islet β-cells from pancreatic tissue for research or therapeutic use.
Detection and diagnosis of diabetes by measuring reduction in islet β-cell mass.
Treatment of diabetes via transplantation of isolated CD39L3-expressing islet β-cells from donors to recipients.
Testing the efficacy of agents designed to increase islet β-cell mass through imaging or immunoassay.
Testing the efficacy of islet β-cell transplants by detecting transplanted cells using anti-CD39L3 antibodies.
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