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WO-2026091010-A1 - METHOD FOR INDUCING PERIPHERAL BLOOD CX3CR1+ POTENTIALLY TUMOR-REACTIVE T CELLS

WO2026091010A1WO 2026091010 A1WO2026091010 A1WO 2026091010A1WO-2026091010-A1

Abstract

The present invention provides a method for inducing peripheral blood CX3CR1+ potentially tumor-reactive T cells. The present invention provides an optimized hot and cold ablation method, which effectively increases the level of potentially tumor-reactive T cells in the peripheral blood of a test animal, thereby improving anti-tumor immune response. The present invention further provides a tumor-reactive T cell population prepared by means of a hot and cold ablation method.

Inventors

  • LIU, PING
  • CHEN, MAN

Assignees

  • 上海美杰医疗科技有限公司

Dates

Publication Date
20260507
Application Date
20241031

Claims (10)

  1. A method for treating cancer in a mammal in need, wherein the mammal has cancerous tissue, the method comprising the steps of: (1) Cold treatment: Cold treatment of one or more cancerous tissues of the mammal, wherein the cold treatment includes reducing the temperature of the treated cancerous tissue to ≤-10°C and maintaining it for 2-20 minutes; (2) Rewarming treatment: The cancerous tissue that had undergone cold treatment was heated to 2-20℃; and (3) Heat treatment: The cancer tissue that has been reheated in the previous step is subjected to heat treatment, which includes raising the temperature of the cancer tissue to 45-60°C and maintaining it for 2-20 minutes.
  2. The method of claim 1, wherein the cancer treatment includes increasing the level of tumor-reactive T cells in the mammal, wherein the tumor-reactive T cells are CX3CR1+ T cells or CX3CR1+GPR56+ T cells.
  3. The method as described in claim 1, wherein the cancer is selected from the group consisting of: liver cancer, colorectal cancer, melanoma, lung cancer, breast cancer, and pancreatic cancer.
  4. The method as described in claim 1 is characterized in that, in step (1), during the cold treatment process, the cancerous tissue is cooled to -10°C to -30°C and maintained for 5 min to 15 min.
  5. The method as described in claim 1, wherein in step (3), during the heat treatment process, the cancerous tissue is heated to 50°C to 55°C and maintained for 10 min to 15 min.
  6. A method for preparing a population of tumor-reactive T cells, characterized in that the method includes the following steps: (1) Cold treatment: A mammal with one or more cancerous tissues is provided, and the cancerous tissues of the mammal are subjected to cold treatment, the cold treatment comprising reducing the temperature of the treated cancerous tissues to ≤-10°C and maintaining it for 2-20 minutes; (2) Rewarming treatment: The cancerous tissue that had undergone cold treatment was heated to 2-20℃; and (3) Heat treatment: The cancer tissue that has been reheated in the previous step is subjected to heat treatment, wherein the heat treatment includes raising the temperature of the cancer tissue to 45-60°C and maintaining it for 2-20 minutes; (4) Collect peripheral blood from the mammal to obtain a population of tumor-reactive T cells.
  7. The method as described in claim 6 is characterized in that, in the tumor reactive T cell population, CX3CR1+ T cells account for ≥20% of the total number of T cells, preferably ≥40%, and more preferably ≥70%.
  8. The method as described in claim 6 is characterized in that, in the tumor reactive T cell population, CX3CR1+GPR56+ T cells account for ≥20% of the total number of T cells, preferably ≥40%, and more preferably ≥70%.
  9. A tumor-reactive T cell population, characterized in that the tumor-reactive T cell population is prepared by the method described in claim 6.
  10. The use of the tumor-reactive T cell population as described in claim 9 in the preparation of a medicament for treating cancer.

Description

A method for inducing peripheral blood CX3CR1+ potential tumor reactive T cells Technical Field This invention relates to the field of biomedicine. Specifically, this invention relates to a method for inducing peripheral blood CX3CR1+ potential tumor reactive T cells. Background Technology For patients with intermediate-stage hepatocellular carcinoma (HCC), local treatment has been identified as the preferred treatment option. Ablation therapy is the primary non-surgical local treatment method. Currently, the most commonly used ablation techniques in clinical practice include cryoablation, radiofrequency ablation (RFA), and microwave ablation (MWA). Ablation therapy can induce local and systemic immune responses, thereby eliminating distant metastatic lesions; this phenomenon is known as the "distant effect." However, studies have shown that ablation-induced immune responses are often weak and insufficient to induce sustained protective anti-tumor immunity. Ablation-induced anti-tumor immunity depends on the release of antigens and damage-associated molecular patterns (DAMPs) resulting from tumor cell immune death. The type and amount of tumor antigens and DAMPs released are influenced by the ablation method and conditions, ultimately leading to the induction of different immune responses. Therefore, it is necessary to optimize ablation methods and conditions to maximize the induced anti-tumor immune response. Summary of the Invention The purpose of this invention is to provide an ablation therapy method that enhances anti-tumor immune response. Another object of the present invention is to provide peripheral blood potential tumor reactive T cells induced by an ablation method. In a first aspect of the invention, a method for treating cancer in a mammal having cancerous tissue is provided, the method comprising the steps of: (1) Cold treatment: Cold treatment of one or more cancerous tissues of the mammal, wherein the cold treatment includes reducing the temperature of the treated cancerous tissue to ≤-10°C and maintaining it for 2-20 minutes; (2) Rewarming treatment: The cancerous tissue that had undergone cold treatment was heated to 2-20℃; and (3) Heat treatment: The cancer tissue that has been reheated in the previous step is subjected to heat treatment, which includes raising the temperature of the cancer tissue to 45-60°C and maintaining it for 2-20 minutes. In another preferred embodiment, the method further includes the step of: (4) Repeat steps (1) to (3) once or multiple times. In another preferred embodiment, the cancer treatment includes increasing the level of tumor-reactive T cells in the mammal. In another preferred embodiment, the tumor-reactive T cells are CX3CR1+ T cells or CX3CR1+GPR56+ T cells. In another preferred embodiment, the tumor-reactive T cells are CX3CR1+GPR56+CD8+ T cells. In another preferred embodiment, the mammals include: humans, orangutans, monkeys, rats, mice, rabbits, or combinations thereof. In another preferred embodiment, the cancerous tissue includes: a tumor, tissue infected with cancer cells, tumor metastases, and blood from a cancer patient. In another preferred embodiment, the cancerous tissue is superficial cancerous tissue or cancerous tissue located within the body. In another preferred embodiment, a non-invasive or minimally invasive method is used in the cold treatment or heat treatment step. In another preferred embodiment, the method further includes monitoring the temperature of the cancerous tissue in steps (1) to (3). In another preferred embodiment, the monitoring of the temperature of cancerous tissue includes contact temperature sensors or non-invasive temperature monitoring, such as temperature monitoring through infrared image analysis, nuclear magnetic resonance temperature detection, or ultrasonic temperature detection. In another preferred embodiment, in the cold treatment in step (1), the cold treatment is to bring a cold source or its delivery device into contact with the epidermis or insert it into the tumor center. In another preferred embodiment, the cold source is liquid nitrogen. In another preferred embodiment, the heat treatment in step (3) is: Contacting the heat source or its transmission device with the epidermis or inserting it into the center of the tumor; or High-frequency electromagnetic field heating. In another preferred embodiment, the delivery device has a contact head with a contact surface for adhering to the cancerous tissue. The cold source cools the cancerous tissue through the contact head, and/or the heat source warms the cancerous tissue through the contact head. In another preferred embodiment, the delivery device includes a treatment probe that can be image-guided to penetrate the center of the tumor. A cold source cools the cancerous tissue through the contact head, and/or a heat source warms the cancerous tissue through the contact head. In another preferred embodiment, the cancerous tissue carried by the mammal