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Motile sperm domain-containing protein 2 and cancer

A technology for cancer and cancer metastasis, applied in the direction of anti-animal/human immunoglobulin, peptide/protein components, medical preparations containing active ingredients, etc., can solve the problem that the biological function of MOSPD2 has not yet been described

Active Publication Date: 2022-04-29
步行免疫治疗公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The biological function of MOSPD2 has not been described

Method used

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  • Motile sperm domain-containing protein 2 and cancer
  • Motile sperm domain-containing protein 2 and cancer
  • Motile sperm domain-containing protein 2 and cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0351] anti-MOSPD2 antibody

[0352] Anti-MOSPD2 polyclonal antibodies were generated according to the following method.

[0353] Materials and methods

[0354] Production and purification of hemagglutinin (HA)-tagged recombinant human MOSPD2 (HA-rhMOSPD2)

[0355]The full-length human MOSPD2 cDNA was inserted into the lentiviral plasmid vector pLVX-EF1α-IRES-Puro (Clonetech, CA) using EcoRI and Xbal restriction sites. An HA-tag encoding oligonucleotide (YPYDVPDYA; SEQ ID NO: 15) was inserted into the N-terminal region of MOSPD2 using an EcoRI restriction site. For transduction, A2058 melanoma cells (ATCC CRL-11147, VA) were spun at 2000 rpm at room temperature in the presence of 8 μg / ml polybrene (Sigma, Israel) and lentiviral particles containing a vector expressing HA-rhMOSPD2 60 minutes. Cells were then seeded in 6-well plates. After 72 hours, fresh medium containing puromycin (4 μg / ml Sigma, Israel) was added for selection of transduced cells. To purify HA-rhMOSPD2,...

Embodiment 2

[0362] MOSPD2 and migration of metastatic cell lines

[0363] To assess the role of MOSPD2 in cancer cell migration, sh-control or sh-MOSPD2 lentiviral particles were used to silence MOSPD2 expression in two melanoma cell lines, A2058 melanoma and MDA-231 breast cancer.

[0364] Specifically, sh-control or sh-MOSPD2-transduced A2058 or MDA-231 cells (3x10 5 ) were inoculated in the upper chamber of a QCM 24-well 5 μm well migration assay plate (Corning-Costar, Corning, NY), followed by 10% FBS / RPMI-1640 and EGF (200 ng / ml, Peprotech Israel) in the lower chamber Incubate in presence for 24 hours. Cells that had migrated to the lower chamber were then stained with crystal violet before images were acquired.

[0365] figure 1 It was confirmed that sh-MOSPD2 lentiviral particles had significantly reduced protein epitopes and inhibited cell migration in vitro.

Embodiment 3

[0367] MOSPD2 and cell proliferation

[0368] To determine whether the inhibition of cell migration following MOSPD2 silencing is secondary to fundamental cellular functions such as proliferation, the proliferation of MDA-231 breast cancer cells transduced with sh-control or sh-MOSPD2 lentiviral particles was tested for 3 days time period.

[0369] Specifically, MDA-231 cells transduced with sh-control or sh-MOSPD2 lentivirus were seeded in 6-well plates (10 4 pieces / hole). Cells were counted by FACS every 24 hours in triplicate for 3 consecutive days.

[0370] exist figure 2 The data shown in indicate that MOSPD2 is not required for the proliferation of these cells, suggesting a regulatory role for MODPD2 specifically in migration.

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Abstract

Disclosed herein is treating, reducing the incidence of one or more activities in or of cancer cells, or preventing one or more activities in or of cancer cells Methods of multiple activities, methods of treating, reducing the incidence of, or preventing migration or metastasis of cancer cells, by reducing tumor-associated macrophages (TAMs) or their migration Methods of treating cancer, reducing the incidence of cancer or preventing cancer, and treating cancer, including metastases, reducing the incidence of cancer, including metastases, for example using inhibitors of motile sperm domain-containing protein 2 (MOSPD2) or Methods of preventing cancer, including metastatic cancer. Also disclosed are inhibitors of MOSPD2 (eg, anti-MOSPD2 antibodies or antigen-binding fragments thereof) and pharmaceutical compositions containing MOSPD2 inhibitors. Also disclosed are methods for predicting, diagnosing, or prognosing cancer, cancer metastasis, tumor progression, or tumor invasion in a subject.

Description

[0001] field of invention [0002] The present invention relates to treating, preventing or reducing the incidence of cancer and metastases, for example treating, preventing one or more activities in or reducing one or more of cancer cells or cancer cells or a method for the incidence of various activities, a method for treating, preventing or reducing the incidence of migration or metastasis of cancer cells, by regulating the migration of tumor-associated macrophages (TAM) to treat, prevent Cancer or methods of reducing the incidence of cancer, and methods of treating, preventing, or reducing the incidence of cancer, including metastases, using motile sperm domain-containing protein 2 (MOSPD2). The invention also relates to pharmaceutical compositions comprising one or more inhibitors of MOSPD2 and to polypeptide inhibitors of MOSPD2 such as antibodies or antigen-binding fragments thereof. The present invention also relates to methods for predicting, diagnosing or prognosing c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/18C07K14/435A61K35/13A61P35/00G01N33/574
CPCG01N33/574G01N33/5017G01N33/5029G01N33/689A61K38/00C07K14/00C07K16/18C07K2317/21C07K2317/54C07K2317/76A61K45/06A61K2039/505A61P35/00C07K16/30A61P35/02A61P35/04A61P43/00C07K2317/92C12Q1/6886C12Q2600/158G01N2333/435G01N33/57492
Inventor I·门德尔O·普罗菲塔-梅兰Y·萨勒姆A·绶哈姆N·阿寇威E·布雷特巴特
Owner 步行免疫治疗公司
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