Engineered Platelets With Split Toxins for Circulating Tumor Cells

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Solution Overview

Problem

Current cancer treatments, particularly for metastatic cancer, are harsh on patients due to systemic side effects and often lead to drug resistance, and there is a need for therapies that can adapt to different patients and eradicate a wide range of tumor cells while minimizing systemic side effects.

Innovation Solution

Engineering megakaryocytes and platelets with nucleic acid constructs containing promoters linked to recombination sites and split toxin sequences flanked by intein sequences, allowing for the production of engineered antibodies that target and destroy circulating tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If systemic therapy such as chemotherapy is used to treat metastatic cancer, then the treatment can reach circulating tumor cells throughout the body, but it causes severe side effects including nausea, vomiting, neuropathy, organ and tissue damage, and immune deficiencies

Engineering Contradiction:

Improvetreatment efficacyVSAvoidsystemic side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent engineers platelets to express specific antibodies against circulating tumor cells, creating a localized therapeutic effect only at the site of tumor cells rather than systemic exposure. The platelets are modified with tumor-specific antibodies (anti-HER2, anti-EGFR, anti-ROR1) that enable targeted recognition and killing of cancer cells while leaving healthy tissues unaffected

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent uses engineered platelets as intermediary carriers to deliver toxic payloads specifically to tumor cells. The platelets act as a mediator between the therapeutic agent and the target, using their natural ability to bind to and engulf tumor cells to deliver the toxin only where needed, thereby avoiding systemic side effects

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If targeted drugs are used to treat cancer, then the treatment can address specific cancer pathways, but patients invariably face relapse and develop drug resistance due to activation of alternative pathways

Engineering Contradiction:

Improvetargeted therapy specificityVSAvoidlong-term treatment effectiveness

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent divides the toxin into two separate inactive fragments (N-terminal and C-terminal halves) that are delivered within the platelet. These fragments are non-toxic individually but become fully active only when reassembled inside the tumor cell, providing a built-in safety mechanism and preventing premature activation or resistance development

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a composite therapeutic system combining engineered platelets with split toxin technology. The platelet serves as a biological carrier that protects and delivers the split toxin fragments, which then reassemble into an active toxin within the target cell, creating a multi-component system that overcomes single-target resistance

Inventive Principle:

Principle #40Composite materials

3Measurement precision

If drugs are designed to target specific cancer biomarkers, then the treatment can be effective for patients with those biomarkers, but drugs may be ineffective or cause severe side effects for patients with different biomarker expressions

Engineering Contradiction:

Improvebiomarker targeting accuracyVSAvoidpatient population coverage

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent engineers platelets to express multiple different tumor-specific antibodies (anti-HER2, anti-EGFR, anti-ROR1) simultaneously, enabling a single therapeutic platform to target multiple different cancer types and biomarker profiles. This multi-functional approach allows the treatment to adapt to different patient populations based on their specific biomarker expressions

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 engineered platelets effectively target and kill circulating tumor cells, potentially reducing metastasis and minimizing systemic side effects by using split toxin sequences that are activated only upon internalization in target cells, thus providing a targeted and effective cancer treatment.

Implementation Method 1

the engineered antibody sequence comprises a split toxin sequence flanked by an intein sequence

Methodology Applied

Scientific EffectProtein splicing:

Data Source

PatentUS12618076B2Methods of engineering platelets for targeting circulating tumor cells

Publication Date: 2026.05.05 UNIV OF UTAH RES FOUND

AI summary

Disclosed herein are nucleic acid constructs that can be used to build genetic circuits for producing antibodies comprising split toxins. Also disclosed herein are methods of producing platelets comprising the antibodies. The platelets produced by the methods disclosed herein can be used to target circulating tumor cells.