CD137 Enrichment for Tumor Infiltrating Lymphocyte Selection
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Solution Overview
Problem
Current methods for isolating and expanding tumor-reactive T-cells for cancer immunotherapy are inefficient, leading to poor activation and limited clinical efficacy due to the challenge of identifying and enriching these cells from tumor tissues.
Innovation Solution
The method involves isolating and culturing CD137+ cells from solid tumor tissue, which includes tumor-infiltrating lymphocytes, cytotoxic T lymphocytes, natural killer cells, and lymphokine-activated killer cells, using cytokines like IL-2, IL-7, and IL-15, and immune cell stimulating ligands such as anti-CD3 and anti-CD28 antibodies to enhance their expansion and activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional methods are used to isolate and expand tumor-reactive T-cells, then the isolation process can be performed, but the efficiency is poor and activation is limited
Solution Approach 1:
The patent extracts and isolates tumor-reactive T-cells from tumor tissue samples using specific immunological markers and culture conditions. By selectively extracting the activated tumor-reactive subset from the mixed T-cell population, the method achieves both high isolation efficiency and reliable activation quality, resolving the technical contradiction between productivity and reliability.
Solution Approach 2:
The patent changes key parameters of the isolation process, including using specific culture media compositions, cytokine combinations (IL-2, IL-7, IL-15), and activation conditions to enhance both the efficiency of isolation and the quality of T-cell activation. These parameter optimizations simultaneously improve productivity and reliability.
2Quantity of substance
If tumor tissue is used as the source, then the frequency of tumor antigen-specific T-cells is higher, but the isolation and expansion process remains inefficient
Solution Approach 1:
The patent performs preliminary activation and enrichment of tumor-reactive T-cells in vitro before expansion. By pre-activating the T-cells with tumor antigens or specific stimuli and selecting for activated markers, the method prepares the cells in advance to enable efficient subsequent expansion, resolving the contradiction between having high frequency cells and achieving high productivity.
3Adaptability or versatility
If ex vivo stimulation with viral antigens is used, then some reactive T-cells can be created, but the T-cells are limited to only virus specific antigens
Solution Approach 1:
Instead of stimulating T-cells with viral antigens to create reactivity (as in conventional methods), the patent inverts the approach by using tumor-derived antigens or tumor cell lines for stimulation. This ensures that the generated T-cell response is specifically directed against tumor antigens rather than viral antigens, resolving the contradiction between adaptability and tumor specificity.
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 allows for the rapid isolation and expansion of tumor-reactive T-cells, enhancing their anti-tumor activity and potency for adoptive immunotherapy, thereby improving cancer treatment outcomes.
Implementation Method 1
using cytokines like IL-2, IL-7, and IL-15, and immune cell stimulating ligands such as anti-CD3 and anti-CD28 antibodies to enhance their expansion and activity
Implementation Method 2
immune cell stimulating ligands such as anti-CD3 and anti-CD28 antibodies
Data Source
AI summary
The invention includes compositions and methods to rapidly isolate and culture cells that are potent for use in adoptive immunotherapy. In one embodiment, the isolated cells of the invention are tumor infiltrating lymphocytes (TIL) that express CD137 (also known as 4-1BB and TNFSFR9).