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Use of non B‑s IgG as a marker for stem/progenitor cells

A nonb-sigg, 1.nonb-sigg technology, applied in the field of biological immunology, can solve problems such as unexplained, undetermined IgG epitope, unanswered role and molecular mechanism, and achieves the effect of great application value.

Active Publication Date: 2018-04-10
BEIJING SIG BIOPHARMACEUTICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

④ Non B-Ig is expressed at a high level and high frequency in a variety of tumor cells; non B-Ig is involved in the growth and survival of tumor cells, and even the occurrence and metastasis of tumors, but the specific role and molecular mechanism have not been answered
However, it does not explain the structure of the antigenic determinant recognized by RP215, that is to say, the antigenic epitope of the IgG cannot be determined
[0007] Although more and more evidence shows that non-B-cell-derived Ig has great application value, due to the limitations of various factors such as research tools and methods, the understanding of non-B-Ig is still very limited, thus limiting its development and application

Method used

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  • Use of non B‑s IgG as a marker for stem/progenitor cells
  • Use of non B‑s IgG as a marker for stem/progenitor cells
  • Use of non B‑s IgG as a marker for stem/progenitor cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 Discovery of sialylated glycosyl sites of non-B cell-derived IgG

[0042] First, Ig (TIg) extracted from tumors and Ig (commercialized IVIG) extracted from normal human venous blood were used as research objects, and a lectin that could bind to sialic acid (Western elderberry agglutinin, Sambucusnigra agglutinin, SNA) was used as the binding protein, or the specific monoclonal antibody RP215 (prepared by the laboratory of Dr. Lee, Canada, and now stored in the Human Disease Gene Research Center of Peking University) was used as the primary antibody. It was found by Western blot that RP215 recognized The bands of the SNA almost completely coincided with the bands recognized by SNA, and its positive signal only showed the slow mobility part in the IgG fraction ( figure 1 A). Further, we used SNA-bound agarose column to affinity-purify the sialylated IgG in IVIG. By Western blot detection, we found that RP215 could better recognize the eluted glycoproteins, and ...

Embodiment 2

[0045] Example 2 Distribution of non B-sIgG in normal tissue and tumor tissue

[0046] After confirming that RP215 only recognizes non-B-IgG sialylated glycosyl sites, we explored the expression profile of non-B-sIgG in normal and tumor tissues.

[0047] (1) Expression of non B-sIgG in normal tissues

[0048] Chips containing different normal tissues were selected, and the expression of nonB-sIgG recognized by RP215 in normal tissues was detected by immunohistochemistry (IHC). It was found that in normal tissues, non B-sIgG was mainly positive in squamous epithelial cells; Epithelium, gastric epithelium and thymus epithelium, etc.) have positive reactions. Notably, however, the basal layer cells of the multilayered epithelium (with adult stem / progenitor properties) were strongly positive. While other tissues, such as muscle, connective tissue, lymphocytes, etc., no positive reaction was found (Table 3).

[0049] In view of the strong positive signal of non B-sIgG in multil...

Embodiment 3

[0059] Example 3 Non B-sIgG is used to evaluate the degree of differentiation of lung adenocarcinoma tumors

[0060] Immunohistochemical staining was performed on 232 cases of lung adenocarcinoma with RP215 monoclonal antibody, and the staining results were scored, combined with clinical case data, for statistical analysis, see Table 3.

[0061] table 3

[0062] pathological features

Number of cases

RP215 staining score mean (SD)

P

age

0.6830

<60

126

23.8(40.5)

≥60

106

25.7(38.3)

gender

0.9926

Female

106

22.8(37.9)

male

126

26.2(40.8)

smoking history

0.2523

do not smoke

28

15.7(40.1)

smoking

33

9.2(26.2)

differentiation

0.0159*

Medium and high differentiation

134

17.6(29.1)

poorly differentiated

94

34.4(49.6)

TNM staging c

0.9253

...

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Abstract

The invention discloses an application of non B-sIgG used as a stem / progenitor cell marker, and especially discloses an application to preparation of an antitumor drug as a therapeutic target of a tumor stem / progenitor cell, and sialylated glycosyl on the IgG does not relate to O-glycosylation. In one application, distribution of this kind of cells can be conveniently detected by preparing antibody, immune cell, protein and micromolecule which can specifically recognize the non B-sIgG and sialylated glycosyl locus. Especially a detection reagent or a targeted medicament aiming at the specific molecule for the tumor stem / progenitor cell is designed for effectively controlling diagnosis, treatment and prognosis evaluation of the tumor, and clinic application value is high.

Description

technical field [0001] The invention relates to the technical field of biological immunology, in particular to non-B cell-derived sialylated IgG and the application of the IgG sialylated glycosyl site as a stem / progenitor cell marker. Background technique [0002] The traditional concept of immunology holds that the source of immunoglobulin (Immunogloubin, Ig) is limited to B lymphocytes and plasma cells, and other somatic cells do not produce Ig molecules because there is no functional gene rearrangement of Ig genes. However, Qiu Xiaoyan's research group reported for the first time at home and abroad that non-B cells, especially tumor cells, can also produce Ig. At present, it is clear that in addition to the classic Ig molecules produced by B cells, there is a class of Ig gene products that have not been discovered so far, which are different from classic Ig in terms of source, structure and function, including IgG, IgA, IgM etc., known as non-B cell-derived Ig (non B-Ig)...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N33/68G01N33/574G01N33/569
CPCG01N33/56966G01N33/5743G01N33/686G01N2400/02
Inventor 邱晓彦廖沁园刘伟刘洋黄晶王宠
Owner BEIJING SIG BIOPHARMACEUTICAL TECH CO LTD
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