Recombinant Phage Constructs for Anti-Cancer Immune Response

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Solution Overview

Problem

Current monoclonal antibody therapies for cancer are costly and unsustainable, particularly for individuals without medical insurance, highlighting the need for affordable active immunotherapies that can stimulate the body to produce its own antibodies against CD47, a protein shielding cancer cells from immune destruction.

Innovation Solution

Development of recombinant bacteriophage constructs that express exogenous peptide sequences to generate immune responses against CD47, including the use of specific amino acid sequences and epitope mimics, which can be administered as vaccines to induce anti-CD47 antibodies, thereby blocking the CD47-SIRPα interaction and promoting phagocytosis of cancer cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If monoclonal antibody therapies are used to block CD47-SIRPα interaction, then cancer treatment effectiveness is improved, but treatment cost increases significantly

Engineering Contradiction:

Improvecancer treatment effectivenessVSAvoidtreatment cost

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs recombinant phage particles as disposable vaccine vehicles that can be produced at low cost through bacterial expression systems. These phage particles deliver CD47 peptide antigens to trigger long-lasting immune responses without requiring expensive monoclonal antibody production, thereby resolving the contradiction between treatment effectiveness and cost.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention stimulates the patient's own immune system to produce endogenous anti-CD47 antibodies through vaccination with recombinant phage constructs. This self-service approach eliminates the need for continuous administration of expensive exogenous monoclonal antibodies, achieving sustained cancer treatment effectiveness at lower cost.

Inventive Principle:

Principle #25Self-service

2Adaptability or versatility

If recombinant phage constructs expressing CD47 peptides are administered, then active immune response against CD47 is stimulated, but selective targeting of cancer cells over normal cells must be ensured

Engineering Contradiction:

Improveimmune response stimulationVSAvoidimpact on normal cells

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent exploits the differential expression levels of CD47 on cancer versus normal cells. By designing vaccine-induced antibodies that recognize CD47, the system achieves selective targeting because cancer cells express CD47 at much higher levels, making them the primary targets of phagocytic attack while normal cells with low CD47 expression remain relatively spared.

Inventive Principle:

Principle #3Local quality

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

The recombinant phage constructs effectively stimulate the production of anti-CD47 antibodies, potentially leading to tumor regression and cancer treatment at a lower cost compared to traditional monoclonal antibody therapies, while being selectively targeted to cancer cells to minimize impact on normal cells.

Implementation Method 1

recombinant bacteriophage constructs that express exogenous peptide sequences and bind to anti-CD47 antibodies

Methodology Applied

Scientific EffectPhage display:

Implementation Method 2

The recombinant phage constructs and the expressed exogenous sequence can be administered to a subject in need thereof in order to generate an immune response against CD47 in the subject, including generating anti-CD47 antibodies

Methodology Applied

Scientific EffectImmune response stimulation:

Implementation Method 3

Binding of CD47 to SIRPα leads to inhibition of phagocytosis... molecules that prevent the CD47-SIRPα interaction such as neutralizing monoclonal antibodies (mAb) against CD47

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 4

CD47 plays a role of a 'don't eat me' signal for phagocytic cells, making cells expressing CD47 resistant to phagocytosis

Methodology Applied

Scientific EffectPhagocytosis:

Data Source

PatentUS20230338462A1Phage-peptide constructs for stimulation of an Anti-cancer immune response against CD47

Publication Date: 2023.10.26 EDWARD VIA COLLEGE OF OSTEOPATHIC MEDICINE AUBURN

AI summary

Disclosed are recombinant bacteriophage constructs and related exogenous peptide sequences for generating immune responses against CD47. The disclosed recombinant phage constructs bind to antibodies against CD47 and can be administered to an animal to generate an immune response against CD47, including generating anti-CD47 antibodies. The disclosed recombinant phage may comprise an amino acid sequence of CD47, epitopic fragments, variants, or functional mimics thereof. Also disclosed are methods for making and selecting such recombinant phage constructs and compositions that comprise such constructs (e.g., compositions for inducing an immune response against CD47 including pharmaceutical or veterinary compositions used as vaccines). Also disclosed are recombinant polynucleotides comprising genomic nucleic acid of the recombinant phage constructs disclosed herein.