TGF-beta Vaccine Polypeptides for Immune Checkpoint Blocker Synergy

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Solution Overview

Problem

Current cancer therapies face challenges in effectively targeting and overcoming the immune-suppressive functions of TGFβ1-expressing cells, which contribute to tumor evasion and reduced efficacy of Immune Checkpoint Blockers.

Innovation Solution

Development of novel polypeptides derived from TGFβ1 that stimulate specific immune responses, targeting TGFβ1-expressing cells, potentially used in conjunction with existing immunotherapies to enhance anti-cancer immune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If TGFβ1 is used to suppress immune responses in cancer therapy, then immune suppression is enhanced, but anti-tumor immune efficacy is reduced

Engineering Contradiction:

Improveimmune suppressionVSAvoidanti-tumor immune efficacy

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses the TGFβ1 protein itself as the antigen to generate immune responses against it. By vaccinating with TGFβ1-derived polypeptides, the harmful immune suppression caused by TGFβ1 is converted into a beneficial anti-TGFβ1 immune response that neutralizes the suppressive effect and enhances anti-tumor immunity

Inventive Principle:

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

Solution Approach 2:

Instead of using TGFβ1 to suppress immunity, the invention inverts the approach by generating immune responses against TGFβ1. The polypeptides are designed to elicit T-cell responses that target and neutralize TGFβ1-expressing cells, reversing the harmful effect into a therapeutic benefit

Inventive Principle:

Principle #13The other way round (Inversion)

2Reliability

If Immune Checkpoint Blockers are used to enhance anti-tumor immunity, then T-cell activation is improved, but efficacy is reduced by TGFβ1-mediated suppression

Engineering Contradiction:

ImproveT-cell activationVSAvoidTGFβ1-mediated immune suppression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces TGFβ1-specific T-cells as an intermediary between Immune Checkpoint Blockers and TGFβ1-expressing cells. These specialized T-cells mediate the neutralization of TGFβ1, allowing ICBs to function effectively by removing the TGFβ1-mediated barrier to T-cell activation

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention applies preliminary anti-action by pre-generating TGFβ1-specific immune responses through vaccination with polypeptides before or alongside Immune Checkpoint Blocker therapy. This preliminary immunity prevents TGFβ1 from suppressing the subsequent ICB-mediated T-cell activation

Inventive Principle:

Principle #9Preliminary anti-action

Data Source

PatentUS20220315634A1TGF-beta vaccine

Publication Date: 2022.10.06 IO BIOTECH APS

AI summary

The present invention relates to novel polypeptides derived from TGFb1. The invention also concerns uses of the polypeptides, polynucleotides encoding the peptides and uses thereof, and compositions comprising the polypeptides and uses thereof.