CD25-Targeted NIR Photoimmunotherapy for Selective Tumor Treg Depletion
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Solution Overview
Problem
Current cancer immunotherapies face challenges in selectively depleting tumor-infiltrating regulatory T cells (Tregs) without affecting other immune cells, leading to systemic adverse effects and reduced therapeutic efficacy.
Innovation Solution
Employing CD25-targeted near-infrared photoimmunotherapy (NIR-PIT) using antibody-IR700 conjugates, specifically binding to CD4+CD25+Foxp3+ Tregs, which are then killed by near-infrared light, while minimizing damage to non-target cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If systemic anti-CD25 antibodies are used to deplete Tregs, then Treg depletion is achieved, but CD25-expressing anti-tumor effector cells are also depleted, reducing therapeutic effectiveness
Solution Approach 1:
The patent applies local quality by making the antibody-mediated Treg depletion spatially selective. The antibody-IR700 conjugate is activated only by NIR light irradiation at the tumor site, creating localized Treg depletion exactly where needed while preserving systemic Treg populations and CD25-expressing effector cells in healthy tissues.
Solution Approach 2:
The patent introduces NIR light as an intermediary that mediates selective activation of the antibody-photoabsorber conjugate. This intermediary enables precise spatial control, allowing Treg depletion only in irradiated tumor regions while leaving other CD25-expressing cells intact in non-irradiated areas.
2Reliability
If immune checkpoint inhibitors are used to inhibit immunosuppressive mechanisms, then anti-cancer immune response is enhanced, but autoimmune side effects occur in normal organs
Solution Approach 1:
The patent applies local quality by restricting immune modulation to the tumor microenvironment through NIR light-activated antibody conjugates. This localized approach enhances anti-cancer immune responses at the tumor site while avoiding systemic immune activation that causes autoimmune side effects in normal organs.
Solution Approach 2:
The patent segments the immune modulation effect spatially by using NIR light to activate antibody-photoabsorber conjugates only in irradiated tumor regions. This segmentation isolates the therapeutic effect to the tumor while protecting normal tissues from autoimmune damage.
3Quantity of substance
If conventional photoimmunotherapy is used to kill target cells, then selective cell death is achieved, but damage to adjoining cells may occur
Solution Approach 1:
The patent applies local quality by using NIR light, which has deeper tissue penetration and more selective activation characteristics compared to visible light. This enables precise spatial control of photoimmunotherapy, killing target cells bound by antibody-IR700 conjugates while minimizing damage to adjoining non-target cells through controlled light delivery.
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
This approach effectively reduces Tregs by at least 50-95% within tumors, enhancing anti-tumor immune responses and reducing tumor volume and metastasis, with minimal impact on non-target cells and systemic toxicity.
Implementation Method 1
Near-infrared photoimmunotherapy (NIR-PIT) is a method of treating cancers that uses activation of an antibody-photoabsorber conjugate activated by near-infrared light to kill cells
Implementation Method 2
NIR-light exposure (690 nm) induces highly selective, necrotic cancer cell death within minutes without damage to adjoining cells
Data Source
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AI summary
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-2.