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Application of androgen deprivation in inhibiting growth of androgen-independent tumors

An androgen and androgen receptor technology, applied in the field of tumor treatment, can solve the problems of immune cell damage, reduced response to antigen stimulation, deterioration, etc., to achieve the effect of promoting treatment, expanding the scope of application, and inhibiting growth

Pending Publication Date: 2022-07-29
北京汇睿微免科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most cancer patients are elderly individuals, and immune senescence leads to a reduced ability of elderly individuals to respond to antigenic stimuli, including tumor antigens
Moreover, this situation is further exacerbated by the damage to immune cells caused by radiation and chemotherapy

Method used

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  • Application of androgen deprivation in inhibiting growth of androgen-independent tumors
  • Application of androgen deprivation in inhibiting growth of androgen-independent tumors
  • Application of androgen deprivation in inhibiting growth of androgen-independent tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1 ADT induces thymus regeneration in aged animals

[0063] 1.1. The total number of thymocytes increased

[0064] The genetic background of all mice used in this example was C57BL / 6J, and the aged mice were 12-18 months old. Leuprolide was intraperitoneally injected at 2 mg / kg, 3 times / week, for a period of 4 weeks, and the saline injection group was used as a control (Control). After the mice were sacrificed, the thymus was harvested, a thymocyte suspension was prepared, and viable cells were counted. The result is as figure 1 As shown, the total number of thymocytes in the Leuprolide-treated group was significantly increased.

[0065] 1.2 The development of thymocytes is generally normal

[0066] According to the expression of CD4 and CD8, the development of thymocytes is divided into three stages: DN, DP and SP. And further based on the expression of CD44 and CD25, DN cells can be divided into four subgroups: DN1:CD25 - CD44 + ;DN2:CD25 + CD44 + ;DN3...

Embodiment 2

[0070] Example 2 The role of ADT in tumor therapy

[0071] Take 1.5~4×10 6 Logarithmic growth phase prostate cancer Rm-1, colon cancer MC-38, lung cancer LLC, liver cancer Hepa1-6 cells were subcutaneously inoculated into 12-18 month old C57BL / 6J old mice. Thereafter, intraperitoneal administration was started: gonadotropin-releasing hormone agonist Leuprolide, 2 mg / kg, and androgen receptor antagonist Flutamide, 50 mg / kg, 3 times a week. The tumor volume (length×width×width / 2) was measured every other day, and the tumor growth status of the mice after administration was observed.

[0072] The above tumor cell lines were cultured in vitro, and different concentrations (1μM, 5μM, 10μM, 15μM) of Flutamide were added to observe the effect on cell growth. Flutamide was used instead of Leuprolide for in vitro culture because the latter must act via the hypothalamic-pituitary-gonadal axis.

[0073] 2.1 The inhibitory effect of ADT on prostate cancer growth is partly dependent on ...

Embodiment 3

[0080] Example 3 Influence of ADT on the anti-tumor effect of immune checkpoint inhibitors

[0081] In this example, androgen-dependent tumors (prostate cancer Rm-1) and androgen-independent tumors (lung cancer LLC cells and liver cancer Hepa 1-6 cells) were used as research objects, and the above tumor cells were subcutaneously inoculated into recipient mice ( All genetic backgrounds were C57BL / 6J, 12-18 months old), and then began intraperitoneal administration: Leuprolide, 2 mg / kg; anti-PD-1, 200 μg / only; all were administered 3 times a week. The tumor volume (length×width×width / 2) was measured every other day, and the tumor growth status of the mice after administration was observed.

[0082] Effects of medication on androgen-independent tumor growth such as Figure 11 As shown, Leuprolide and anti-PD-1 each inhibited lung cancer LLC cells ( Figure 11 A) and liver cancer Hepa 1-6 cells ( Figure 11 B) The growth of the transplanted tumor has an inhibitory effect, and m...

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Abstract

The invention relates to the technical field of tumor treatment, in particular to application of androgen deprivation in inhibiting growth of androgen-independent tumors. The invention finds that the androgen deprivation therapeutic agent can play a role in treating androgen-independent tumors by reconstructing the function of senescent thymus, and further provides a new application of the androgen deprivation therapeutic agent; the invention also finds that the androgen deprivation therapeutic agent and the immune checkpoint inhibitor can generate a synergistic effect in the treatment of the androgen-independent tumor, so that the growth of the androgen-independent tumor is more effectively inhibited, a new strategy is provided for the treatment of the androgen-independent tumor, and the application of the androgen deprivation therapeutic agent and the immune checkpoint inhibitor in the treatment of the androgen-independent tumor is promoted. A foundation is laid for expanding the application range of anti-androgen therapy, and a thought is provided for developing a new strategy of tumor immunotherapy.

Description

technical field [0001] The invention relates to the technical field of tumor treatment, in particular to the application of androgen deprivation in inhibiting androgen-independent tumor growth. Background technique [0002] The progressive decline of immune system function with age leads to increased susceptibility to pathogens, decreased responsiveness to vaccines, and increased risk of cancer and autoimmune diseases. The hallmark changes of immunosenescence include: 1) a decrease in naïve lymphocytes and an increase in the proportion of memory cells; 2) a decrease in the ability to respond to neoantigen stimuli; and 3) persistent low-level inflammation. Although immunosenescence affects all aspects of the immune system, T lymphocytes and the immune response mediated by them are most severely affected. In elderly individuals, the number of initial T cells and the diversity of the T cell receptor (TCR) pool were significantly reduced, while the proportion of memory T cells ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K45/06A61K39/395A61P35/00
CPCA61K45/00A61K45/06A61K39/3955A61P35/00A61K2300/00
Inventor 张毓魏望知陈增款
Owner 北京汇睿微免科技有限公司
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