CD47 Blockade and Anti-VEGF Combination for Lower-Dose Tumor Control
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Solution Overview
Problem
Existing CD47 blockade therapies for cancer treatment, such as those using SIRPα-based agents, often require high doses to be effective and may have limitations in binding to red blood cells, necessitating strategies to manage agent 'sink' after administration.
Innovation Solution
Combining a CD47-blocking form of SIRPαFc with an anti-VEGF agent, such as bevacizumab, at sub-therapeutic doses, enhances cancer cell depletion by synergistic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of CD47-blocking SIRPαFc are used to achieve effective cancer cell depletion, then anti-cancer effect is improved, but agent consumption increases and cost rises
Solution Approach 1:
The patent combines CD47-blocking SIRPαFc with anti-VEGF agents (bevacizumab or ranibizumab) to create a synergistic combination therapy. This merging of two different mechanisms allows achieving effective cancer cell depletion at lower doses of each agent, thereby reducing overall agent consumption while maintaining or improving anti-cancer effect.
2Reliability
If high doses of CD47-blocking SIRPαFc are administered to overcome the agent 'sink' effect from red blood cell binding, then sufficient drug reaches target cells, but off-target binding to red blood cells increases
Solution Approach 1:
The patent introduces anti-VEGF agents as intermediaries that work synergistically with CD47-blocking SIRPαFc. The anti-VEGF component addresses tumor vasculature and creates a multi-modal approach, allowing the CD47 blocker to work more efficiently at lower doses, thereby reducing off-target binding to red blood cells while maintaining effective drug delivery to cancer cells.
3Quantity of substance
If monotherapy with CD47-blocking SIRPαFc is used at sub-therapeutic doses to minimize side effects, then agent consumption is reduced, but anti-cancer effect is insufficient
Solution Approach 1:
The patent merges CD47-blocking SIRPαFc with anti-VEGF agents to create a synergistic combination where sub-therapeutic doses of each component achieve therapeutic effects when combined. The anti-VEGF agent enhances the anti-cancer effect of the CD47 blocker, allowing reduced agent consumption while maintaining sufficient anti-cancer effect.
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
The combination of CD47-blocking SIRPαFc and anti-VEGF agents achieves superior anti-cancer effects, even at doses that are ineffective alone, by improving cancer cell depletion and tumor control.
Implementation Method 1
antibodies that bind to cancer cell antigens, and through recruitment and activation of macrophages by way of Fc receptor binding to the Fc portion of that antibody
Implementation Method 2
an agent that binds vascular endothelial growth factor (an anti-VEGF agent), such as the anti-VEGF antibody bevacizumab
Implementation Method 3
inhibition of the CD47/SIRPα interaction (CD47 blockade) will allow macrophages to 'see' and destroy the target CD47+ cancer cell
Data Source
AI summary
Various forms of cancer and other diseases are treated using a medicinal combination of a SIRPαFc to block binding with CD47, and an anti-VEGF agent such as humanized antibody bevacizumab to control vascularization.