Complement Antagonists Inhibit PKB to Induce Apoptosis in C3aR/C5aR Cancer Cells

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Solution Overview

Problem

Current cancer therapies are inadequate in effectively inducing apoptosis in neoplastic cells expressing C5aR or C3aR, as they rely on blocking intrinsic complement regulators and enhancing C5a-C5aR and C3a-C3aR interactions, which has limitations in killing tumor cells and reducing metastases.

Innovation Solution

Administering complement antagonists to reduce or inhibit protein kinase B (PKB) activity in cancer cells expressing C5aR or C3aR, thereby blocking the interaction of C3a or C5a with their respective receptors, which disrupts the AKT signaling pathway and induces apoptosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current cancer therapies block intrinsic complement regulators and enhance C5a-C5aR and C3a-C3aR interactions, then tumor cell susceptibility to killing is improved, but the effectiveness in inducing apoptosis and reducing metastases deteriorates

Engineering Contradiction:

Improvetumor cell susceptibility to killingVSAvoidapoptosis induction effectiveness

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent changes the therapeutic approach from enhancing C5a-C5aR and C3a-C3aR interactions to blocking these interactions using complement antagonists. This parameter change in the mechanism of action enables effective apoptosis induction and metastasis reduction while maintaining tumor cell susceptibility through alternative pathways

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent inverts the conventional approach by instead of enhancing C5a-C5aR and C3a-C3aR interactions to kill tumor cells, it blocks these interactions using complement antagonists. This inversion reveals a more effective pathway for inducing apoptosis and reducing metastases

Inventive Principle:

Principle #13The other way round (Inversion)

2Productivity

If complement antagonists are administered to block C5a-C5aR and C3a-C3aR interactions, then apoptosis induction is improved, but the mechanism of action becomes more complex

Engineering Contradiction:

Improveapoptosis induction effectivenessVSAvoidmechanism of action complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts and targets the specific C5aR and C3aR receptors on cancer cells using complement antagonists. By focusing on these specific receptors rather than the entire complement system, the mechanism becomes more targeted and controllable, reducing overall system complexity while maintaining effectiveness

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses complement antagonists as intermediary molecules that specifically bind to C5aR and C3aR receptors. These intermediaries mediate the blocking effect, providing a controlled and specific mechanism that simplifies the overall therapeutic approach compared to non-specific complement activation

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS8940299B2Method of treating cancer

Publication Date: 2015.01.27 CASE WESTERN RESERVE UNIV

AI summary

A method for inducing apoptosis of a neoplastic cell expressing C3aR or C5aR includes administering at least one complement antagonist to the cell so that the at least one complement antagonist substantially reduces or inhibits the activity of protein kinase B in the neoplastic cell.