SIRPα-CD47 Blockade for MDSC Differentiation in Cancer Immunotherapy

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Solution Overview

Problem

Current therapeutic approaches to modulate myeloid-derived suppressor cells (MDSC) are inefficient and have adverse secondary effects, and there is no method to specifically target and differentiate MDSC into non-suppressive cells without affecting other cell populations, which is crucial for treating conditions associated with MDSC accumulation, such as cancer and chronic infections.

Innovation Solution

A compound that blocks the interaction between signal regulatory protein alpha (SIRPa) and CD47 is used to differentiate MDSC into non-suppressive lymphoid cells, particularly into effector cells like NK cells, by inhibiting their immunosuppressive functions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapeutic approaches are used to modulate MDSC, then some immunosuppressive function is reduced, but the approaches are inefficient and have adverse secondary effects

Engineering Contradiction:

Improveefficacy of MDSC modulationVSAvoidadverse secondary effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the molecular target parameter from general MDSC modulation to specific SIRPa blocking. By targeting the SIRPa-CD47 interaction pathway, the therapy achieves more reliable and specific MDSC differentiation into non-suppressive cells, reducing adverse effects on other cell populations while improving therapeutic efficacy.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If non-specific MDSC modulation is applied, then immunosuppression is reduced, but other cell populations are affected adversely

Engineering Contradiction:

Improveimmunosuppression reductionVSAvoideffect on other cell populations

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by targeting a specific molecular interaction (SIRPa-CD47) that is selectively expressed on MDSC. This localized targeting approach allows differentiation of MDSC into non-suppressive cells while preserving the functions of other cell populations, as the SIRPa-CD47 pathway is not universally expressed across all immune cells.

Inventive Principle:

Principle #3Local quality

3Reliability

If MDSC differentiation into non-suppressive cells is achieved, then immune responses are enhanced, but the method complexity increases

Engineering Contradiction:

Improveimmune response enhancementVSAvoidmethod complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses an intermediary approach by employing a compound that blocks the SIRPa-CD47 interaction as a mediator to induce MDSC differentiation. This blocking compound acts as a therapeutic agent that simplifies the overall method by providing a direct mechanism to transform MDSC into non-suppressive cells, enhancing immune responses without requiring complex multi-step protocols.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentEP3783027B1Method and compositions for inducing differentiation of myeloid derived suppressor cell to treat cancer

Publication Date: 2025.12.03 OSE IMMUNOTHERAPEUTICS SA

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AI summary

The present invention pertains to the field of immunotherapy. More specifically, the present invention provides a method for treating a patient having a cancer by administering a compound blocking the interaction between SIRPa and CD47. The administration of the compound blocking the interaction between SIRPa and CD47, reduces the MDSC-induced immunodepression and consequently allow appropriate immune responses in cancers.