Hydroxycitrate T Cell Culture for Persistence and Antitumor Activity
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Solution Overview
Problem
Existing adoptive cell therapy (ACT) using cancer-reactive T cells faces challenges such as decreased in vivo persistence, survival, and antitumor activity, as well as increased apoptosis, which hinder effective cancer treatment.
Innovation Solution
Culturing isolated T cells in vitro with hydroxycitric acid or its salts, such as potassium hydroxycitrate, to enhance T cell populations, increasing persistence, antitumor activity, and reducing apoptosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If T cells are cultured using conventional methods, then T cell production is achieved, but in vivo persistence and survival decrease
Solution Approach 1:
The patent changes the chemical composition parameter of the culture medium by adding hydroxycitric acid and its salts, which modifies T cell metabolism and phenotype to improve in vivo persistence and survival characteristics
Solution Approach 2:
The patent applies preliminary cultural conditioning of T cells with hydroxycitric acid before adoptive transfer, which pre-adapts the T cells to in vivo conditions and enhances their persistence and survival capabilities after transplantation
2Productivity
If T cells are cultured using conventional methods, then T cell expansion is achieved, but antitumor activity decreases
Solution Approach 1:
The patent modifies the culture medium composition by incorporating hydroxycitric acid, which alters T cell metabolic pathways to maintain antitumor activity during expansion, producing T cells with both high proliferation capacity and sustained cytotoxic function
3Productivity
If T cells are cultured using conventional methods, then T cell proliferation is achieved, but apoptosis increases
Solution Approach 1:
The patent changes the biochemical environment by adding hydroxycitric acid, which modulates apoptotic signaling pathways in T cells, allowing for robust proliferation while simultaneously reducing activation-induced cell death and improving overall cell survival
Data Source
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AI summary
Provided are methods of producing an isolated population of T cells, the method comprising culturing isolated T cells in vitro in the presence of hydroxycitric acid, and/or a salt thereof, wherein the salt is potassium hydroxycitrate or sodium hydroxycitrate. Also provided are related isolated populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer in a mammal.