Anti-CD3 Immunotoxin for Immune Retraining in CD3-Negative Cancers

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current cancer treatments lack effective methods for providing long-term immune protection against cancers that do not bear or uniformly bear CD3 epitopes, and existing immunomodulatory agents often cause autoimmune diseases due to breaking immune tolerance to self-antigens.

Innovation Solution

Administering anti-CD3 immunotoxins to deplete T-cells, allowing repopulation with new T-cells in the presence of non-CD3 cancer antigens, thereby retraining the immune system to recognize and attack cancer cells without breaking tolerance to self-antigens, using immunotoxins like A-dmDT390-bisFv (UCHT1) for immunomodulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If existing immunomodulatory agents are used to stimulate the immune system, then long-term anti-cancer protection is achieved, but autoimmune diseases develop due to breaking immune tolerance to self antigens

Engineering Contradiction:

Improvelong-term anti-cancer protectionVSAvoidautoimmune diseases

Core Design Contradiction:

Duration of action of moving objectVSObject-generated harmful factors

Solution Approach 1:

The patent applies this principle by using anti-CD3 immunotoxins, originally designed to kill CD3-bearing cancer cells, to instead achieve immunomodulation. The toxin's harmful cytotoxic effect is converted into a beneficial immune-resetting mechanism that eliminates exhausted T cells and enables repopulation with cancer-recognizing T cells, without breaking tolerance to self antigens

Inventive Principle:

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

Solution Approach 2:

The patent changes the functional parameter of the anti-CD3 immunotoxin from direct cancer cell killing to immune system modulation. By controlling the dosage and treatment protocol, the toxin selectively depletes certain T cell populations while preserving immune tolerance mechanisms, thereby achieving long-term protection without autoimmune side effects

Inventive Principle:

Principle #35Parameter changes

2Speed

If immunotoxins are used to kill cancer cells directly, then immediate cancer cell destruction occurs, but long-term immune protection is not achieved

Engineering Contradiction:

Improveimmediate cancer cell destructionVSAvoidlong-term immune protection

Core Design Contradiction:

SpeedVSDuration of action of moving object

Solution Approach 1:

The patent applies preliminary action by first using the immunotoxin to clear exhausted and non-functional T cells from the immune system before allowing repopulation with new T cells. This preparatory depletion creates space and conditions for new T cells to develop and become educated to recognize cancer antigens, thereby establishing long-term immunity

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The immunotoxin serves as an intermediary agent that mediates between the immune system and cancer cells. Rather than directly killing cancer cells, it indirectly facilitates long-term protection by modulating T cell populations and enabling the immune system to develop its own anti-cancer response

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If immunomodulatory agents are used to reset the immune system, then tumor regression occurs over time, but the treatment course is prolonged and unpredictable

Engineering Contradiction:

Improvetumor regressionVSAvoidprolonged treatment course

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent employs periodic action through structured immunotoxin administration protocols that create controlled cycles of T cell depletion and repopulation. This periodic modulation accelerates the immune reset process and creates more predictable tumor regression patterns compared to continuous or irregular immunomodulatory treatment

Inventive Principle:

Principle #19Periodic action

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

This approach provides long-term immune protection against cancer, preventing recurrence and metastasis without causing autoimmune diseases, as the immune system is retrained to recognize and destroy cancer cells effectively, while maintaining tolerance to self-antigens.

Implementation Method 1

immunotoxins comprise antigen-binding domains of an anti-CD3 antibody and a portion of the diphtheria toxin protein

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 2

the toxic portion of the molecule then kills the cell to which it is bound

Methodology Applied

Scientific EffectToxin-mediated cell killing:

Implementation Method 3

administering anti-CD3 immunotoxins to modulate the immune systems of such patients and achieve long-term immune protection

Methodology Applied

Scientific EffectImmune system modulation:

Implementation Method 4

allowing repopulation and maturation of new T cells in the patient in the presence of non-CD3 cancer cell antigens

Methodology Applied

Scientific EffectImmune recognition:

Data Source

PatentUS11098120B2Immunomodulation by anti-CD3 immunotoxins to treat cancers bearing or not uniformly bearing surface CD3

Publication Date: 2021.08.24 ANGIMMUNE LLC

AI summary

Methods of modulating the immune systems of patients suffering from cancers that do not bear, or do not uniformly bear, surface CD3 are provided. The methods involve administering an anti-CD3 immunotoxin (e.g. A-dmDT390-bisFv(UCHT1)), to the patient so as to cause the patient's immune system to recognize and destroy non-CD3 cancer cells.