Targeting CD47 to Induce Cancer Stem Cell Differentiation

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Solution Overview

Problem

Current cancer therapies are ineffective in targeting and eliminating cancer stem cells, which are responsible for tumor recurrence and metastasis due to their ability to evade immune clearance through elevated CD47 expression, leading to challenges in developing effective treatments.

Innovation Solution

The use of agents that alter CD47 signaling, such as anti-CD47 antibodies like B6H12, peptide 7N3, or CD47-targeted CRISPR constructs, to induce differentiation of cancer stem cells, thereby down-regulating EGFR and up-regulating tumor suppressor genes, promoting irreversible differentiation and reducing metastasis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional cancer therapies are used, then differentiated tumor cells are killed, but cancer stem cells survive and cause tumor recurrence

Engineering Contradiction:

Improvetumor cell elimination efficiencyVSAvoidtumor recurrence prevention

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

Instead of directly killing cancer stem cells through conventional cytotoxic approaches, the patent inverts the strategy by blocking the CD47 'don't eat me' signal, thereby enabling macrophages to naturally phagocytose and eliminate cancer stem cells through enhanced clearance mechanisms

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent introduces macrophages as intermediary cells that mediate the elimination of cancer stem cells. Anti-CD47 antibodies serve as mediators that enhance the interaction between macrophages and cancer stem cells, facilitating selective clearance of the therapy-resistant stem cell population

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If CD47 expression is elevated on cancer stem cells, then immune clearance is evaded, but targeted therapy can be developed

Engineering Contradiction:

Improveimmune evasion capabilityVSAvoidtherapeutic targetability

Core Design Contradiction:

Object-affected harmful factorsVSAdaptability or versatility

Solution Approach 1:

The patent converts the harmful effect of elevated CD47 expression (immune evasion) into a beneficial therapeutic target. By developing anti-CD47 antibodies, the elevated CD47 on cancer stem cells becomes the very marker that enables selective targeting and elimination of these therapy-resistant cells through macrophage activation

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If cancer stem cells are targeted for elimination, then tumor recurrence is prevented, but selective targeting is challenging

Engineering Contradiction:

Improvetumor recurrence preventionVSAvoidcancer stem cell identification

Core Design Contradiction:

ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent exploits the local quality difference in CD47 expression levels between cancer stem cells (high expression) and differentiated tumor cells (lower expression). This differential expression pattern enables selective targeting of cancer stem cells by anti-CD47 antibodies, allowing precise identification and elimination of the therapeutic target population

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20210355495A1Methods to eliminate cancer stem cells by targeting CD47

Publication Date: 2021.11.18 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Described herein is the discovery that cancer stem cells (CSCs) can be induced to differentiate by altering CD47 signaling. Provided herein are methods and compositions for inducing differentiation of cancer stem cells, for instance irreversible differentiation, including methods of treating subjects with cancer such as breast cancer, colon cancer, lung cancer, ovarian cancer, or melanoma, and including metastatic as well as primary cancer. Also provided are methods for treating subjects with triple negative breast cancers involving forcing differentiation of bCSCs of the subjects through targeting of CD47.