Innate Immune Cell Compositions for Off-the-Shelf Immunotherapy

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Solution Overview

Problem

Current immunotherapies relying on adaptive immune cells, such as alpha.beta T cells, face challenges including graft versus host disease, lengthy manufacturing processes, and cytokine release syndrome, limiting their use as an 'off-the-shelf' solution for a wide patient population.

Innovation Solution

Development of compositions enriched in innate immune cells like NK cells and gamma.delta T cells, which are activated and expanded ex vivo without feeder cells, using specific polypeptides and cytokines to achieve high activation levels and tailored ratios, enabling an 'off-the-shelf' immunotherapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If adaptive immune cells (alpha.beta T cells) are used for immunotherapy, then specific immune response is improved, but manufacturing time and complexity increase

Engineering Contradiction:

Improvespecific immune responseVSAvoidmanufacturing time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

Instead of using adaptive immune cells that require lengthy manufacturing, the patent inverts the approach by using innate immune cells (gamma.delta T cells and NK cells) that provide rapid response without requiring HLA matching or extended culture periods, thereby resolving the contradiction between specificity and manufacturing time

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent changes the cell type parameter from adaptive (alpha.beta T cells) to innate (gamma.delta T cells and NK cells), which fundamentally alters the manufacturing timeline and complexity while maintaining therapeutic efficacy through alternative mechanisms of action

Inventive Principle:

Principle #35Parameter changes

2Reliability

If adaptive immune cells are used for immunotherapy, then targeted antigen recognition is improved, but risk of graft versus host disease and cytokine release syndrome increases

Engineering Contradiction:

Improvetargeted antigen recognitionVSAvoidgraft versus host disease and cytokine release syndrome

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs innate immune cells that function as disposable, short-lived therapeutic agents providing rapid cytotoxic activity against target cells without the persistence and immunogenicity issues of adaptive immune cells, thereby reducing the risk of graft versus host disease and prolonged cytokine release

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent converts the traditionally viewed limitation of innate immune cells (lack of antigen specificity) into a benefit by using their non-specific cytotoxic mechanisms to avoid the harmful effects of adaptive cell persistence and HLA-mediated graft versus host reactions

Inventive Principle:

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

3Reliability

If alpha.beta T cells are used for immunotherapy, then adaptive immune response is improved, but ease of manufacture and universal application decreases

Engineering Contradiction:

Improveadaptive immune responseVSAvoidoff-the-shelf availability

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent achieves universality by using innate immune cells that do not require HLA matching or patient-specific customization, allowing a single product to be manufactured and stored for use with multiple patients without compromising therapeutic effectiveness

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent implements preliminary action by manufacturing and storing innate immune cell products in advance before patient need, eliminating the requirement for rapid on-demand production that plagues adaptive cell therapies

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20210380944A1Therapeutic preparations of gamma-delta t cells and natural killer cells and methods for making and using them

Publication Date: 2021.12.09 OSPEDALE PEDIATRICO BAMBINO GESU OPBG

AI summary

Provided are methods of making innate immune cell compositions containing gamma.delta (γδ) T cells and/or Natural Killer (NK) cells, and the resulting compositions and related products of manufacture and kits for use in cancer and infectious disease therapy. The methods provided herein permit tailoring of the relative amounts of gamma.delta (γδ) T cells and Natural Killer (NK) cells in the compositions. for cellular therapies against a wide variety of cancers and infectious diseases. The resulting compositions can further be used to generate compositions containing either NK cells alone or gamma.delta T cells alone, for immune cellular therapies. The compositions provided herein also can be genetically altered: the gamma delta T cells and Natural Killer cells are modified to express chimeric antigen receptors (CARs) or exogenous T cell receptors (TCRs), which can be used to target any cell surface molecule either directly or indirectly, e.g., a marker on a cancer cell or an infected cell.