Plexin D1 Targeting for Tumor Vascular Disruption
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-angiogenic therapies for tumors have limited success in clinical settings due to mature vasculature insensitivity and angiogenesis-independent growth of metastases, necessitating a targetable protein for effective vascular targeting therapy.
Innovation Solution
Plexin D1 is identified as a targetable protein expressed on tumor blood vessels and activated macrophages, allowing for the use of specific binding molecules to interfere with its function or expression for therapeutic and diagnostic purposes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-angiogenic therapy is used to inhibit tumor growth, then tumor growth is inhibited in animal models, but clinical translation is less successful due to mature vasculature insensitivity
Solution Approach 1:
The patent targets a specific local characteristic of tumor vasculature - the expression of plexin D1 on endothelial cells - rather than attempting to inhibit all angiogenesis pathways. This localized targeting approach allows selective disruption of tumor blood vessels while potentially sparing normal vasculature, addressing the insensitivity of mature vessels to conventional anti-angiogenic therapies.
Solution Approach 2:
The invention changes the therapeutic parameter from inhibiting VEGF signaling to blocking plexin D1 function. By targeting a different molecular parameter (plexin D1 receptor) that is specifically expressed on tumor endothelial cells, the therapy overcomes the insensitivity problem associated with mature vasculature that has adapted to VEGF inhibition.
2Reliability
If anti-angiogenic therapy is applied, then primary tumor growth may be controlled, but metastatic growth continues via co-option of pre-existent vessels
Solution Approach 1:
The plexin D1 target serves multiple functions: it is involved in both de novo angiogenesis and in the co-option process where pre-existent vessels are recruited by tumors. By targeting plexin D1, the therapy simultaneously addresses both angiogenic vessel formation and co-option of existing vessels, providing universal coverage against different metastatic mechanisms.
3Reliability
If vascular targeting therapy is implemented, then tumor blood supply can be disrupted, but specific markers for tumor vasculature are needed
Solution Approach 1:
The patent uses antibodies that specifically recognize and bind to plexin D1 on tumor endothelial cells as a copy or surrogate marker system. These antibodies serve as detectable markers that specifically identify tumor vasculature expressing plexin D1, enabling both detection and targeted delivery of therapeutic agents to the tumor blood supply.
Data Source
AI summary
The present invention relates to plexin D1 for use as a targetable protein in the treatment or diagnosis of disorders that involve expression of plexin D1. Diagnosis is suitably effected by detecting the presence of plexin D1 in the body or a bodily tissue or fluid, whereas treatment is effected by targeting plexin D1 for delivery of therapeutics to the site where treatment is needed. The invention further relates to the use of molecules that bind plexin D1, a nucleic acid encoding plexin D1 or a ligand of plexin D1 for the preparation of a therapeutical composition for the treatment or diagnosis of disorders that involve expression of plexin D1. The disorders comprise disorders in which plexin D1 is expressed on tumor cells, tumor blood vessels or activated macrophages.