Compositions comprising il-31 and uses thereof

a technology of il-31 and compositions, applied in the field of compositions comprising il-31, can solve the problems of increased angiogenesis and metastasis, tumor re-growth and even metastasis, and achieve the effect of preventing or reducing metastasis, reducing or preventing metastasis

Inactive Publication Date: 2017-03-16
TECHNION RES & DEV FOUND LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0007]This application is directed to a method for treating cancer and / or preventing or reducing metastasis comprising the step of administering IL-31, a fused protein comprising IL-31, an agent which up-regulates IL-31, an IL-31 receptor agonist or a complex comprising either IL-31 or a fused protein that comprises IL-31 to a subject in need, thereby treating cancer and / or reducing or preventing metastasis.

Problems solved by technology

Cancer is a leading cause of death in most countries, and the result of billions of dollars in healthcare expense around the world.
One of the main obstacles in clinical oncology is that tumors can usually resist therapy, leading to tumor re-growth and even metastasis.
It has been demonstrated that several types of bone marrow derived cells home-in on chemotherapy-treated tumors and colonize there, leading to increased angiogenesis and metastasis.

Method used

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  • Compositions comprising il-31 and uses thereof
  • Compositions comprising il-31 and uses thereof
  • Compositions comprising il-31 and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

IL-31 Affects Tumor Cell Proliferation and Viability

[0151]Cell lysates from tumor cell lines including EMT6, P3, MPC, CT26, B16, LLC, K7M2, 4T1 and MC38 were analyzed for IL-31 as well as IL-31 receptor (IL-31R) expression using western blot.

[0152]As detailed herein and as presented in FIG. 1(A-G), IL-31 inhibits tumor cell proliferation in IL-31 dependent manner FIG. 1A shows cell lysates from tumor cell lines that were analyzed for IL-31 as well as IL-30 receptor (IL-31R) expression using western blot analysis. Particularly, the results in FIG. 1A show that while IL-31 was highly expressed in MC38 and K7M2 cell lines, it was minimally expressed in P3, MPC, B16 and 4T1 cells. In addition, IL31R shows high expression patterns in most non-metastatic cells when compared to highly metastatic cells which shows low expression pattern.

[0153]Next, MC38 and 4T1 cell lines were used as two representative cells which either express IL-31 or not, respectively, in order to further evaluate the ...

example 2

Lack of IL-31 in Tumor Cells Promotes Tumor Growth and Angiogenesis

[0154]To further confirm the activity of IL-31 on tumor cells in vivo, IL-31 was silenced in MC38 cells using RNAi technique.

[0155]As related to in detail herein, FIG. 2 presents shRNA for IL-31 inhibits the expression of IL-31 in tumor cells. FIG. 2A shows lysates of MC38 murine colon carcinoma cells after they were stably transfected with scramble plasmid or plasmid containing shRNA for IL-31 were evaluated for IL-31 expression using western blot analysis. The graph in FIG. 2B shows the percentage of reduction in IL31 expression in MC38 shIL-31 after it was normalized to its expression in scrambled control MC-38, as assessed by densitometry.

[0156]As can be seen in FIG. 2B, the expression level of IL-31 in MC38 shIL-31 cells was reduced by more than 60% compared to scrambled MC38 control cells.

[0157]As further detailed herein, FIG. 3 presents the lack of IL-31 expression promotes tumor growth, angiogenesis and TAMs....

example 3

IL-31 Induces Anti-Tumor Activity in Both MC38 and 4T1 Tumors

[0160]As detailed herein, FIG. 4 present inhibition of tumor growth, angiogenesis, and metastasis by IL-31. Two million of MC38 cells were implanted into the flanks of C57Bl / 6 mice and half a million 4T1 cells were implanted into the mammary fad pad of BALB / c mice and were left to grow until they reached 150-200 mm3, at which point the mice were implanted with minipumps containing PBS (control) or 0.7 μg / day recombinant IL-31 (rIL-31). Tumor growth was assessed regularly for (FIG. 4A) MC-38 and (FIG. 4B) 4T1. To test whether adding recombinant IL-31 can inhibit the growth of tumors, both MC38 cells, which are known to express IL-31, as well as 4T1 cells, which do not express IL-31, were used. To this end, two million MC38 cells were subcutaneously implanted into the flanks of C57 / Black mice (n=5 / group) and half a million 4T1 cells were orthotopically implanted into the mammary fad pad of BALB / c mice (n=5 / group). When tumor...

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Abstract

A method for treating cancer and/or preventing or reducing metastasis or treating angiogenesis related disorders comprising as the step of administering IL-31 or peptide which is at least about 70%, homologous to the IL-31 sequence as set forth in SEQ ID No. 1.

Description

BACKGROUND OF THE INVENTION[0001]Cancer is a leading cause of death in most countries, and the result of billions of dollars in healthcare expense around the world. It is now well established that a variety of cancers are caused, at least in part, by genetic abnormalities that result in either the overexpression of cancer causing genes, called “oncogenes,” or from loss of function mutations in protective genes, often called “tumor suppressor” genes. One of the main obstacles in clinical oncology is that tumors can usually resist therapy, leading to tumor re-growth and even metastasis. There are many reasons that may explain why tumor cells become resistant to anti-cancer drugs, such as the ability of tumor cells to undergo selection for acquired resistance.[0002]It has been demonstrated that several types of bone marrow derived cells home-in on chemotherapy-treated tumors and colonize there, leading to increased angiogenesis and metastasis.[0003]The contribution of host cells to tum...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/20A61K9/127C07K14/54
CPCA61K38/20C07K14/54C07K2319/30C07K2319/50A61K9/1273A61K39/39A61K2039/55527C12N15/113C07K2319/33C12N15/1136C12N2310/14C12N2310/531
Inventor FREMDER, ELLAARONHEIM, AMISHAKED, YUVAL
Owner TECHNION RES & DEV FOUND LTD
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