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Application of lenalidomide or analogue thereof as immunomodulator

A technology of lenalidomide and its analogues, which is applied in the direction of medical preparations containing active ingredients, anti-inflammatory agents, biological tests, etc., can solve problems such as failure to obtain better therapeutic effects, achieve enhanced response, enhanced immune response, Effects that promote activation or proliferation

Pending Publication Date: 2022-04-26
SHANGHAI TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the prior art, the combined use of lenalidomide and PD-1 antibody did not achieve a good therapeutic effect.

Method used

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  • Application of lenalidomide or analogue thereof as immunomodulator
  • Application of lenalidomide or analogue thereof as immunomodulator
  • Application of lenalidomide or analogue thereof as immunomodulator

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] Example 1 Lenalidomide or its analogues costimulate Crbn lacking CD28 receptors I391V mouse T cells

[0077] 1. Mouse model construction

[0078] (1) Cd28 + / + Crbn + / + Mouse model construction

[0079] Cd28 + / + Crbn + / + Mice are CD28-containing mice containing wild-type Crbn gene. In the present invention, any known Cd28 can be used + / + Crbn + / + mice.

[0080] (2)Cd28 - / - Crbn + / + Mouse model construction

[0081] Cd28 - / - Crbn + / + The mice were CD28-deficient mice containing wild-type Crbn gene. In the present invention, any known Cd28 can be used - / - Crbn + / + Mice, the Cd28 used in the present invention - / - Crbn + / + Mice were provided by the group of teacher Xu Chenqi, Chinese Academy of Sciences.

[0082] (3)Cd 28+ / + Crbn I391V and Cd 28- / - Crbn I391V model building

[0083] Humanized mouse Cd 28+ / + Crbn I391V and Cd 28- / - Crbn I391V For the construction of the model, refer to the patent document 202110302848.X of our research gr...

Embodiment 2

[0091] Embodiment 2 Lenalidomide or its analogues in Cd28 - / - Crbn I391V Enhanced antitumor immunity and suppressed tumor growth in mice

[0092] 1. Construction of MC38-OVA cell line

[0093] In order to construct a suitable tumor model, the present invention first constructed a MC38-OVA cell line with higher immunogenicity on the basis of the mouse colon cancer cell line MC38. The specific implementation process is as follows:

[0094] 1. Construction of recombinant vector pLenti 6.3-OVA

[0095] 1.1 Design chicken ovalbumin OVA (Ovalbumin) sequence

[0096] OVA was first synthesized by Suzhou Jinweizhi Biotechnology Co., Ltd., the sequence is as SEQ ID No.1, as follows:

[0097]

[0098] Among them, __ represents the fragment that is finally expressed in tumor cells.

[0099] 1.2 Connection of chronic viral vector DLenti6.3-CMV-MCS and VOA fragments

[0100] The chronic viral vector pLenti6.3-CMV-MCS (from WuXi Apptec.) was digested with BamHI-HF / XhoI enzyme, and...

Embodiment 3

[0130] Example 3 Lenalidomide or its analogs enhance the response of B16F10-OVA mouse melanoma to PD-1 antibody

[0131] The present invention selects the B16F10-OVA mouse melanoma model that cannot respond to PD-1 antibody monotherapy for experiments, and determines the + / + Crbn I391V The effect of lenalidomide on the efficacy of PD-1 antibody was tested in mice.

[0132] The present invention constructs the B16F10-OVA cell line on the basis of B16F10. For the construction process and method, see Example 2 MC38-OVA cell line construction. After the B16F10-OVA cell line was obtained, the present invention used the cell line to construct a B16F10-OVA mouse melanoma subcutaneous tumor model, and tried lenalidomide and PD-1 antibody (Bio X cell, Cat#BE0146) Combined therapy.

[0133] The specific steps are as follows: Subcutaneously inject B16F10-OVA mouse melanoma cells into Cd28 + / + Crbn I391V Mouse forelimb axilla (2x10^6cells / mouse), on the 4th day after inoculation of...

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Abstract

The invention belongs to the field of biological medicines, and discloses an application of lenalidomide or an analogue thereof in serving as an immunomodulator, the lenalidomide or the analogue thereof is used for co-stimulating CD28-T cells deficient in CD28, enhancing T cell immune response, promoting T cell activation or proliferation, promoting T cell apoptosis, promoting T cell apoptosis and promoting T cell apoptosis. The response of a disease focus infiltrating the CD28-T cells to the immune checkpoint inhibitor is enhanced, the treatment effect of the immune checkpoint inhibitor on diseases is recovered, and the application prospect is wide.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to the application of lenalidomide or its analogues as immunomodulators, in particular to the use of lenalidomide or its analogues in enhancing infiltration of CD28 - Application of T cells in tumor patient response to immunotherapy. Background technique [0002] T cell activation is a crucial link in the tumor immune cycle. In the process of T cell activation, T cell receptor (T cell receptor, TCR) first needs to recognize antigen peptide-MHC molecule complex (pMHC) to produce antigen Signal (Signal1), and secondly, co-stimulatory receptors on the surface of T cells are required to interact with their ligands to generate a series of co-stimulatory signals (Signal 2), and these signals work together to ensure that T cells are fully activated. The co-stimulatory signals that regulate T cell activation are mainly mediated by two types of protein molecules: the immunoglobulin superfamily (Im...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68A61K31/40A61K45/06A61P37/04A61P35/00A61P35/02A61P31/00A61P29/00
CPCG01N33/6872G01N33/56972A61K31/40A61K45/06A61P37/04A61P35/00A61P35/02A61P31/00A61P29/00A61K2300/00
Inventor 仓勇耿晨露彭博
Owner SHANGHAI TECH UNIV
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