GPI-anchored Antigen Modification for Enhanced Immunogenicity

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Solution Overview

Problem

Glycophosphatidylinositol (GPI)-anchored tumor-associated antigens (TAAs) are poorly immunogenic due to their membrane anchoring, making them ineffective targets for cancer immunotherapy.

Innovation Solution

Modification of GPI-anchored antigens by replacing their GPI anchor with one or more transmembrane domains and a cytoplasmic tail sequence derived from proteins that traffic to the endosomal or lysosomal system, such as CD1a, CD1c, or Lamp1, to enhance their immunogenicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If GPI anchor is used to anchor antigen to cell membrane, then antigen is stably positioned on cell surface, but antigen immunogenicity is reduced

Engineering Contradiction:

Improveantigen stability on cell surfaceVSAvoidreduced immunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the anchoring parameter from GPI anchor to transmembrane domain, fundamentally altering how the antigen is attached to the cell membrane. This parameter change enables the antigen to be internalized through endocytosis while maintaining stable cell surface positioning, thereby resolving the contradiction between stability and immunogenicity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces an intermediary mechanism (transmembrane domain with specific cytoplasmic tail sequence) that mediates between the antigen and the cell membrane. This intermediary enables not only stable anchoring but also active internalization via endocytosis, allowing the antigen to access intracellular pathways that enhance immunogenicity while maintaining cell surface presence

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If transmembrane domain replaces GPI anchor, then antigen immunogenicity is enhanced, but antigen residence time on cell surface is reduced

Engineering Contradiction:

Improveenhanced immunogenicityVSAvoidresidence time on cell surface

Core Design Contradiction:

Object-affected harmful factorsVSDuration of action of stationary object

Solution Approach 1:

The patent applies dynamics by designing a transmembrane domain with a cytoplasmic tail sequence that enables active, regulated internalization through endocytosis. This dynamic mechanism allows the antigen to cycle between cell surface and intracellular compartments, maintaining both enhanced immunogenicity (through internalization) and adequate cell surface residence time (through recycling)

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent incorporates a pre-designed cytoplasmic tail sequence in the transmembrane domain that is specifically configured to facilitate endocytic internalization. This preliminary structural arrangement ensures that once the antigen is expressed on the cell surface, it automatically undergoes controlled internalization, balancing immunogenicity enhancement with sustained cell surface presence

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20250179217A1Enhanced Immunogenicity For GPI-anchored Antigens

Publication Date: 2025.06.05 NANTBIOSCIENCE INC

AI summary

Compositions and methods are presented that allow for an enhanced immune response against a GPI-anchored tumor associated antigen by modification of the protein portion of the TAA to include a transmembrane domain and a trafficking signal that directs the modified protein to the endosomal or lysosomal compartment. Most preferably, the modified protein will no longer have a GPI anchor or GPI attachment sequence.