Whole-Cell Antigen Nanoparticles for Specific T Cell Isolation
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Solution Overview
Problem
Current methods for isolating cancer cell-specific T cells from tumor-infiltrating lymphocytes are inefficient, leading to limited therapeutic effects due to the presence of non-specific T cells and regulatory T cells, which can promote tumor growth.
Innovation Solution
A cell system using nanoparticles or microparticles loaded with whole-cell antigens of cancer cells to activate and isolate cancer cell-specific T cells in vitro, followed by expansion and infusion into patients, utilizing specific surface markers for isolation and employing cytokines and antibodies to enhance activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If T cells are isolated and expanded from tumor-infiltrating lymphocytes using conventional methods, then the quantity of T cells increases, but the purity of cancer cell-specific effector T cells remains low due to presence of non-specific T cells and regulatory T cells
Solution Approach 1:
The patent applies preliminary action by using nanoparticles loaded with whole-cell antigens to pre-activate cancer cell-specific T cells before isolation. This activation step occurs in advance of the sorting process, enabling subsequent specific marker-based isolation to effectively separate activated effector T cells from non-specific and regulatory T cells, thus resolving the contradiction between quantity expansion and purity maintenance
Solution Approach 2:
The patent uses nanoparticles as an intermediary carrier to deliver whole-cell antigens to T cells. These nanoparticles act as a mediator that enables specific recognition and activation of cancer cell-specific T cells without directly causing harm to other cell types, thereby allowing selective expansion and isolation of the desired cell population while maintaining overall safety and efficacy
2Quantity of substance
If regulatory T cells are expanded in vitro and infused back into patients, then the quantity of immunotherapy cells increases, but tumor growth is promoted instead of inhibited
Solution Approach 1:
The patent applies the taking out principle by specifically isolating and removing regulatory T cells and non-specific T cells from the expanded T cell population. Through marker-based sorting after nanoparticle activation, only cancer cell-specific effector T cells are selected for infusion, extracting the harmful regulatory T cells from the mixture and preventing their tumor-promoting effects while maintaining the therapeutic quantity of beneficial cells
Solution Approach 2:
The patent applies local quality by creating functionally distinct T cell populations through selective activation. The nanoparticles induce specific activation markers only on cancer cell-specific T cells, creating a locally differentiated state that enables subsequent selective isolation. This local quality change allows the same T cell population to have different fates: activated effector cells are isolated for therapy, while non-activated regulatory cells are left behind
3Device complexity
If conventional T cell isolation methods are used without nanoparticle activation, then the process is simpler, but the ability to specifically identify and isolate cancer cell-specific effector T cells is insufficient
Solution Approach 1:
The patent uses preliminary activation with nanoparticle-antigens to induce specific surface marker expression on cancer cell-specific T cells before isolation. This pre-treatment step creates measurable differences between target cells and non-target cells, enabling subsequent flow cytometry or magnetic sorting to precisely identify and isolate the desired population despite the added complexity of the activation step
Data Source
AI summary
A cell system and an application thereof, and a method for activating a broad-spectrum cancer cell-specific T cell. The cell system includes a cancer cell-specific T cell extracted from a tumor-infiltrating lymphocyte, where the extraction includes steps of co-incubating the tumor-infiltrating lymphocyte or a T cell in the tumor-infiltrating lymphocyte and an antigen-presenting cell with a nanoparticle and/or a microparticle loaded with a whole-cell antigen of a cancer cell to activate a cancer cell-specific T cell, and then isolating the activated cancer cell-specific T cell from the tumor-infiltrating lymphocyte. The problem that broad-spectrum and polyclonal cancer cell-specific T cells in tumor-infiltrating lymphocytes cannot be effectively screened in clinical practice at present is overcome, broad-spectrum effector cancer cell-specific T cells with a specific tumor-killing function can be isolated from the tumor-infiltrating lymphocytes, which have the characteristics of easy isolation and high specificity, and can be used for cancer prevention and treatment.