Anti-4-1BB Antibodies for CD8+ T Cell Isolation and Proliferation
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Solution Overview
Problem
Current methods for isolating and proliferating antigen-specific CD8+ T cells have low recovery and proliferation rates due to the low affinity of tetramers or pentamers, which limits their effectiveness in cancer treatment.
Innovation Solution
The use of humanized anti-4-1BB antibodies to isolate and proliferate antigen-specific CD8+ T cells, which are then cultured with CMV or EBV peptides and IL-2, allowing for a higher recovery and proliferation rate compared to conventional methods using tetramers or pentamers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tetramers or pentamers are used to isolate antigen-specific CD8+ T cells, then the isolation method is established, but the recovery rate and proliferation rate are low
Solution Approach 1:
The patent changes the isolation parameter from using tetramers/pentamers (which have low affinity) to using anti-4-1BB antibodies (which have high affinity and costimulatory activity). This parameter change in the binding mechanism resolves the contradiction by maintaining isolation effectiveness while dramatically improving recovery rate and proliferation rate through the high-affinity interaction between anti-4-1BB antibodies and 4-1BB receptors on activated CD8+ T cells
Solution Approach 2:
The patent introduces anti-4-1BB antibodies as an intermediary substance that mediates the isolation process. These antibodies serve dual functions: they bind to 4-1BB receptors on antigen-specific CD8+ T cells for isolation, and simultaneously provide costimulatory signals that enhance cell proliferation. This intermediary resolves the contradiction by transforming a passive isolation tool into an active proliferative agent
2Ease of manufacture
If conventional isolation methods are used, then the process is established, but the effectiveness for cancer treatment is limited
Solution Approach 1:
The patent changes the biological activity parameter of the isolation reagent from inert (tetramers/pentamers) to actively costimulatory (anti-4-1BB antibodies). This parameter change enables the isolated cells to exhibit enhanced antitumor activity and therapeutic effectiveness while maintaining ease of manufacture through established antibody coating techniques
Solution Approach 2:
The patent converts the potential harm of limited treatment effectiveness into benefit by using anti-4-1BB antibodies that not only isolate but also actively stimulate and proliferate the therapeutic cells. The costimulatory activity, which could be seen as an additional variable, becomes a beneficial feature that enhances both cell expansion and antitumor efficacy
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
The method achieves a high recovery and proliferation rate of antigen-specific CD8+ T cells, overcoming the limitations of conventional techniques and enabling their effective use in cancer treatment without side effects.
Implementation Method 1
a method of isolating antigen-specific CD8+ T cells using anti-4-1BB antibodies, which comprises: culturing peripheral blood mononuclear cells with a peptide antigen to induce activation of antigen-specific CD8+ T cells; isolating the activated antigen-specific CD8+ T cells using anti-4-1BB antibodies
Data Source
AI summary
Provided are methods of isolating and proliferating antigen-specific CD8+ T cells using anti-4-1BB antibodies. The methods of isolating and proliferating CD8+ T cells may yield cells at a higher recovery rate than a conventional isolation method, and the isolation method using humanized anti-4-1BB antibodies may also yield cells at a high recovery rate. Further, in cell culture, cells may be grown at a high proliferation rate. The antigen-specific CD8+ T cells yielded according to the isolation and proliferation methods may be used to treat cancer without any side-effects.