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CN-121987644-A - Application of thiamine pyrophosphate in enhancing anti-tumor function of T cells and CAR-T cells

CN121987644ACN 121987644 ACN121987644 ACN 121987644ACN-121987644-A

Abstract

The invention discloses application of thiamine pyrophosphate in enhancing anti-tumor functions of T cells and CAR-T cells, belongs to the technical field of biological medicines, and relates to application of thiamine pyrophosphate as a cell enhancer of the T cells and the CAR-T cells, wherein the thiamine pyrophosphate can promote cell proliferation, inhibit cell exhaustion, promote cell secretion and kill cell factors related to cancer cells, and further enhance the anti-tumor functions of the T cells and the CAR-T cells in vitro and in vivo. The present invention provides a new strategy for improving T cell or CAR-T cell based cellular immunotherapy.

Inventors

  • ZHU HAICHUAN
  • ZHANG ZIJIAN
  • YU QINGRUN

Assignees

  • 湖北工业大学

Dates

Publication Date
20260508
Application Date
20260312

Claims (7)

  1. 1. Use of thiamine pyrophosphate for the preparation of T-cell and/or CAR-T cell potentiators which promote T-cell and/or CAR-T cell proliferation and/or inhibit T-cell and/or CAR-T cell depletion.
  2. 2. Use of thiamine pyrophosphate as T-cell and/or CAR-T-cell enhancer for the preparation of a product for improving the antitumor function of T-cells and/or CAR-T-cells.
  3. 3. Use according to claim 2, said product having at least the following effects: inhibit T cell and/or CAR-T cell depletion; Promoting T cells and/or CAR-T cells to secrete cytokines associated with killing cancer cells.
  4. 4. The use of claim 1, wherein the CAR-T cells include, but are not limited to, CAR-T cells targeting GPC3, epcam, claudin18.2, HER2, BCMA, CD20, CD22, CD30, CD70, egfrvlll, CD19, or MSLN.
  5. 5. The use according to claim 1, wherein the product comprises a pharmaceutical, a nutraceutical, a food.
  6. 6. Application of thiamine pyrophosphate combined T cells and/or CAR-T cells in preparing antitumor drugs.
  7. 7. The use according to claim 6, wherein the medicament further comprises pharmaceutically acceptable excipients.

Description

Application of thiamine pyrophosphate in enhancing anti-tumor function of T cells and CAR-T cells Technical Field The invention relates to the technical field of medicines, in particular to application of thiamine pyrophosphate (Thiamine pyrophosphate, TPP) in enhancing anti-tumor functions of T cells and CAR-T cells. Background T cells (T lymphocytes) are critical cells in the adaptive immune system and play an essential role in recognizing and eliminating infected cells, cancer cells, and coordinating immune responses. T cells provide highly specific and memory immune responses, are able to distinguish "self" and "non-self" precisely, and produce customized responses to different pathogens or cancer cells. T cells recognize and respond to very small amounts of specific antigens by virtue of the specificity of TCRs. Once activated, they are able to proliferate, differentiate into effector T cells, perform killing, helper or suppressor functions, etc. Memory T cells ensure that the body rapidly initiates a strong secondary immune response when it encounters the same pathogen again, which is also the basis for vaccination to prevent disease. Although T-cell immunity is powerful and delicate, it also faces many challenges under certain pathological conditions, limiting its effective functioning. Under the pathological conditions of chronic infection or continuous antigen exposure of cancers and the like, the T cells gradually lose the effector functions and enter a depletion state. Depleted T cells exhibit reduced cytokine secretion, reduced proliferative capacity, reduced cytotoxicity, and high expression of inhibitory receptors such as PD-1. The tumor microenvironment is a highly immunosuppressive environment, and is rich in suppressive cells (e.g., regulatory T-cell Tregs, myeloid-derived suppressor cell MDSCs, tumor-associated macrophage TAMs), immunosuppressive cytokines (e.g., TGF-beta, IL-10), and metabolites (e.g., lactate, kynurenine). These factors act together to inhibit T cell infiltration, activation, effector function, etc. The activation, proliferation and function of T cells require large amounts of energy and biosynthetic precursors, so their metabolic pathways are critical to their fate and function. In recent years, enhancement of the function of T cells by regulating their metabolism, both against antitumor immunity and investigating their role in autoimmunity, has become a research hotspot. Cellular immunotherapy is an innovative treatment aimed at eliminating cancer using the human immune system, where chimeric antigen receptor T-cell immunotherapy (i.e. CAR-T therapy) is revolutionary, as it produces a very effective and long lasting clinical response. However, CAR-T cell depletion is a short plate present in cellular immunotherapy, characterized by reduced proliferation and cytotoxicity, and up-regulation of inhibitory receptor expression, mainly induced by continuous stimulation of chronic antigens or by a strong signal of CAR self-aggregation. Therefore, the search for new strategies to improve T cell, CAR-T cell function by metabolite small molecule remodeling deserves further investigation, and the enhancement of the anti-tumor function of T cells, CAR-T cells by metabolic compounds has great potential in cancer treatment. Thiamine pyrophosphate, also known as thiamine diphosphate, is a cofactor for enzymes such as pyruvate dehydrogenase, transketolase, and pyruvate decarboxylase, involved in physiological processes such as energy metabolism, carbohydrate metabolism, and oxidative stress. At present, no report of thiamine pyrophosphate inhibiting the depletion of T cells and CAR-T cells and enhancing the anti-tumor capability of the T cells and the CAR-T cells is found. Disclosure of Invention In view of the technical problems in the background art, the invention provides a strategy for improving the functions of T cells and/or CAR-T cells by using thiamine pyrophosphate, and aims to solve the problems of insufficient anti-tumor capability and the like of the depletion of the T cells and/or the CAR-T cells in cellular immunotherapy. The technical scheme of the invention is as follows: in a first aspect, the invention provides the use of thiamine pyrophosphate for the preparation of a T cell and/or CAR-T cell enhancer which promotes T cell and/or CAR-T cell proliferation and/or inhibits T cell and/or CAR-T cell depletion. Preferably, in the above application, thiamine pyrophosphate is used at a concentration of 1-10. Mu.M. In a second aspect, the invention provides the use of thiamine pyrophosphate as T-cell and/or CAR-T-cell enhancer for the preparation of a product for enhancing the antitumor function of T-cells and/or CAR-T-cells, which product may be a medicament, a health product, a food product or the like, and which at least by action enhances the antitumor function of T-cells and/or CAR-T-cells: Promoting proliferation of T cells and/or CAR-T cells; inhibit T cell and/or CAR