LGAM Tracer PET Imaging for Cytotoxic T Cell Activity
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Solution Overview
Problem
Current imaging technologies, such as CT and MRI, are inadequate for differentiating tumor homeostasis from concurrent processes like inflammation or bleeding in glioma patients, and they fail to provide early assessment of tumor response to immunotherapy, leading to delayed prognostic evaluations and variable treatment outcomes.
Innovation Solution
A method using PET or SPECT imaging with a tracer comprising an antibody or antigen-binding fragment specific to the luminal domain of LGAM proteins, such as CD107a, labeled with a detectable moiety to identify cytotoxic T cell activity, allowing for timely evaluation of immunotherapy efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current imaging technologies (CT, MRI, PET) are used to assess tumor response, then tumor localization and size can be detected, but they cannot differentiate tumor homeostasis from concurrent processes like inflammation or bleeding, and cannot provide early assessment of immunotherapy response
Solution Approach 1:
The patent uses LGAM proteins as intermediary markers that specifically indicate cytotoxic T cell activity. These proteins are released during T cell-mediated tumor cell lysis and serve as a direct biochemical mediator between the immunotherapy action and the imaging detection system, enabling specific identification of therapeutic response mechanisms that conventional imaging cannot detect
Solution Approach 2:
The patent detects changes in LGAM protein concentration and distribution as a new imaging parameter. By measuring the presence and quantity of these specific proteins through PET/SPECT imaging, the system transforms the unobservable biological process of T cell activity into a quantifiable imaging parameter that provides early and specific response assessment
2Loss of time
If conventional imaging tools are used, then tumor size and burden changes can be detected, but prognostic evaluation is delayed for weeks or months after treatment initiation
Solution Approach 1:
The patent enables preliminary detection of immunotherapy response by detecting LGAM protein release that occurs early in the therapeutic process. This allows prognostic evaluation to be performed before significant changes in tumor size occur, providing timely information for treatment decision-making rather than waiting for late-stage anatomical changes
3Reliability
If immunotherapy is administered to glioma patients, then a promising therapeutic strategy is provided, but response rates are highly variable and lack of informative biomarkers prevents effective monitoring
Solution Approach 1:
The patent replaces the mechanical/anatomical measurement system (CT, MRI based on physical structure changes) with a molecular/biochemical detection system that targets specific proteins (LGAMs) released during T cell activity. This substitution enables detection of the actual biological mechanism of action at the molecular level, providing reliable and specific response assessment independent of tumor size changes
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables non-invasive, efficient assessment of cytotoxic T cell activity in response to cancer immunotherapy, facilitating early detection of treatment effectiveness and guiding therapy adjustments, thereby potentially improving patient survival rates.
Implementation Method 1
The tracer comprises an antibody or antigen-binding fragment thereof that specifically binds to a luminal domain of a LGAM and is labeled with a PET or SPECT detectable moiety
Implementation Method 2
positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging
Implementation Method 3
positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging
Implementation Method 4
The tracer comprises an antibody or antigen-binding fragment thereof that specifically binds to a luminal domain of a LGAM
Data Source
AI summary
Provided herein is a method for identifying cytotoxic T cell activity due to cancer immunotherapy in a subject. In some embodiments, the method comprises administering an effective amount of a tracer for positron emission tomography (PET) or single photon emission computed tomography (SPECT) to a subject receiving a cancer immunotherapy, wherein the tracer comprises an antibody or antigen-binding fragment thereof that specifically binds to a luminal domain of a lymphocytic granule-associated molecule (LGAM) labeled with a PET or SPECT detectable moiety, and detecting the signal of the tracer by PET or SPECT imaging to identify the cytotoxic T cell activity due to immune therapy for the cancer in the subject. In several embodiments, the antibody or antigen binding fragment specifically binds to the luminal domain of CD107a.