Lrp1 binding agents and uses thereof

An LRP-1, binding domain technology, applied in the field of LRP1 binding agents and their uses, can solve the problems of drug production, no anti-tumor activity, limited efficacy and the like

Inactive Publication Date: 2020-01-03
CHILDRENS MEDICAL CENT CORP
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  • Summary
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  • Description
  • Claims
  • Application Information

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Problems solved by technology

One of the major disadvantages of microenvironment-targeted therapies is that they do not have direct antitumor activity, and thus their efficacy as monotherapy has been limited
Conversely, the main disadvantage of targeted therapy and chemotherapy with direct antitumor activity is that, in addition to unintended deleterious side effects, patients develop resistance to the drugs

Method used

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  • Lrp1 binding agents and uses thereof
  • Lrp1 binding agents and uses thereof
  • Lrp1 binding agents and uses thereof

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Embodiment

[0110] Cancer progression to the metastatic stage is a major contributor to its lethality. In order for a tumor to form lethal metastases, it must enter the vasculature or lymphatic system (intravasation), survive transport, exit blood vessels or lymphatics (extravasation), and proliferate at the metastatic site [1]. During this process, heterotypic signaling between the tumor and its microenvironment can affect tumor growth by regulating the production and secretion of factors that mediate tumor growth, angiogenesis, and immune response. Two proteins, prosaposin and PRSS2, were identified by a functional proteomics screen designed to identify secreted proteins that regulate Tsp-1 in the microenvironment [2]. Prosaposin is preferentially expressed by weakly metastatic tumors and stimulates Tsp-1 in the tumor microenvironment. Conversely, PRSS2 is preferentially expressed by highly metastatic cells and suppresses Tsp-1 expression in the tumor microenvironment. Tsp-1 specifica...

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Abstract

The present invention provides agents tgat hind to binding domain I of LRP1 and mimic the activity of prosaposin in stimulating Tsp-1. Further provided herein are agents that inhibit the function (e.g., the ability to repress Tsp-1) of Protease, Serine 2 (PRSS2) by inhibiting the binding of PRSS2 to LRP1. Methods of using these agents in treating cancer are also provided.

Description

[0001] related application [0002] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 62 / 475,133, filed March 22, 2017, entitled "LRP1 BINDINGAGENTS AND USES THEREOF," the entire contents of which are incorporated herein by reference middle. Background technique [0003] The current standard of care for cancer patients consists of broad acting cytotoxic agents (chemotherapy), radiation, and targeted therapeutics targeting specific secreted proteins, cell surface receptors or kinases. Historically, there have been two classes of therapeutic agents that target the tumor microenvironment, anti-angiogenic drugs (which are limited to anti-VEGF therapy) and immunomodulatory drugs. One of the major drawbacks of microenvironment-targeted therapies is that they do not have direct antitumor activity, and thus their efficacy as monotherapy has been limited. On the contrary, the main disadvantage of targeted therapy and chemotherapy with dir...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395C07K16/30
CPCA61P35/00A61K39/001102A61K38/1709A61K38/12C07K14/705A61K2300/00C07K16/28A61K39/3955
Inventor 伦道夫·S·瓦特尼克
Owner CHILDRENS MEDICAL CENT CORP
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