Chimeric Molecules Targeting uPAR for Cancer Treatment
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Solution Overview
Problem
Current cancer treatment options, such as radiation therapy and chemotherapy, are limited in effectiveness for late-stage cancers and associated with significant side effects, necessitating the development of targeted therapies that can selectively target cancer cells with reduced toxicity.
Innovation Solution
The development of chimeric compounds that bind to the urokinase-type plasminogen activator receptor (uPAR) on cancer cells, recruiting native antibodies to induce immune-mediated destruction through antibody-dependent cellular phagocytosis and cytotoxicity, thereby inhibiting cancer cell growth and metastasis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional chemotherapy and radiation therapy are used to treat cancer, then cancer cells can be killed, but significant side effects and toxicity occur
Solution Approach 1:
The invention segments the therapeutic function into two distinct components: a targeting module (uPAR-binding small molecule) that specifically binds to cancer cells, and a cytotoxic module (antibody) that executes the killing function. This segmentation allows the targeting component to guide the cytotoxic component exclusively to cancer cells, avoiding damage to healthy tissues and reducing systemic toxicity while maintaining effective cancer cell destruction.
Solution Approach 2:
The uPAR-binding small molecule acts as an intermediary that bridges the gap between the immune system and cancer cells. It recruits endogenous antibodies to the cancer cell surface by binding to uPAR, thereby mediating the interaction between the immune system and the tumor. This intermediary approach enables selective cancer cell targeting through the patient's own immune system, reducing the need for directly toxic chemotherapy agents.
2Reliability
If traditional chemotherapy is used to treat late-stage cancer, then some cancer cells may be killed, but effectiveness is limited
Solution Approach 1:
The invention leverages the patient's own immune system to perform the cancer cell destruction function. By recruiting endogenous antibodies through the uPAR-binding small molecule, the therapy enables the immune system to self-target and self-destruct cancer cells. This self-service mechanism overcomes the limitations of chemotherapy by harnessing the body's natural ability to recognize and eliminate abnormal cells, potentially improving effectiveness in late-stage cancer where chemotherapy efficacy diminishes.
3Reliability
If non-selective cancer therapy is used, then cancer cells can be destroyed, but healthy cells are also damaged
Solution Approach 1:
The invention applies local quality by concentrating the therapeutic effect exclusively at the cancer cell surface through specific binding to uPAR. The uPAR-binding small molecule ensures that the recruited antibodies are localized only to cancer cells expressing uPAR, creating a highly localized therapeutic effect. This spatial specificity prevents damage to healthy cells that do not express the target antigen, thereby maintaining high cancer cell killing capability while protecting healthy tissues.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These compounds effectively target uPAR-overexpressing cancer cells, disrupting native uPA-uPAR interactions and redirecting immune functions to selectively destroy cancer cells, potentially reducing toxicity and improving treatment outcomes for metastatic and drug-resistant cancers.
Implementation Method 1
recruit native antibodies of the patient or subject where the antibodies can selectively remove, destroy, clear and/or deactivate targeted cancer cells through antibody-dependent cellular phagocytosis (ADCP)
Implementation Method 2
antibody-dependent cellular cytotoxicity (ADCC)
Implementation Method 3
complement dependent cytotoxicity (CDC)
Data Source
AI summary
The present invention relates to chimeric (including bifunctional) compounds, compositions comprising those compounds and methods of treating cancer in a patient or subject, especially including metastatic and other cancers where cancer cells exhibit overexpression (heightened expression) of cell surface urokinase-type plasminogen activator receptor (urokinase receptor) compared to normal (non-cancerous) cells. The compounds bind to the urokinase-type plasminogen activator receptor (uPAR) on the surface of a cancer cell, including a metastatic cancer cell, and consequently recruit native antibodies of the patient or subject where the antibodies can selectively degrade and/or deactivate targeted cancer cells through antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) against a large number and variety of cancers, thus providing cancer cell death and an inhibition of growth, elaboration and/or metastasis of the cancer, including remission and cure of the patient's cancer.