PRAME Antigen Nucleic Acid Vaccine Vector Design

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Solution Overview

Problem

Current cancer vaccines face limitations due to poor antigen expression in vivo, necessitating the development of safe and effective vaccines that can induce immune responses against cancer cells expressing PRAME antigens to improve cancer treatment and prevention outcomes.

Innovation Solution

The development of nucleic acid molecules encoding PRAME antigens, incorporated into vectors like plasmids or viral vectors, which are designed to induce specific immune responses by eliciting cellular and humoral immune reactions, combined with adjuvants such as IL-12, IL-15, or RANTES, to enhance immunogenicity and overcome immune suppression mechanisms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing cancer vaccines are used, then tumor prevention and treatment are attempted, but antigen expression in vivo is poor leading to limited effectiveness

Engineering Contradiction:
Improveeffectiveness of cancer vaccineVSAvoidantigen expression level
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent modifies the antigen expression system by using nucleic acid molecules encoding PRAME antigens delivered via vectors (plasmids or viral vectors) to enhance antigen expression levels in vivo. This changes the delivery and expression parameters of the antigen, transforming the poor antigen expression problem into effective antigen presentation that induces robust immune responses.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If PRAME antigen is targeted to break immune tolerance, then immune response against cancer cells is induced, but immune suppression mechanisms must be overcome

Engineering Contradiction:
Improveimmune response inductionVSAvoidimmune suppression
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses vectors as intermediaries to deliver PRAME antigen-encoding nucleic acids into host cells. These vectors act as mediators that facilitate antigen expression and presentation, enabling the immune system to recognize and respond to PRAME-expressing cancer cells while overcoming immune suppression mechanisms through enhanced antigen availability.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If nucleic acid molecules encoding PRAME antigens are used, then specific immune responses are induced, but vaccine complexity increases

Engineering Contradiction:
Improvespecificity of immune responseVSAvoidvaccine structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the vaccine into distinct functional components: nucleic acid molecules encoding PRAME antigens, vectors for delivery (plasmids or viral vectors), and adjuvants (such as IL-12, IL-15, or RANTES). This segmentation allows each component to perform its specific function - antigen encoding, delivery, and immune response enhancement - thereby achieving high specificity while managing complexity through modular design.

Inventive Principle:
Principle #1Segmentation

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 vaccines effectively induce robust immune responses, including increased interferon-gamma levels and cytotoxic T-cell activity, leading to enhanced tumor control and improved survival rates by breaking immune tolerance and targeting PRAME-expressing cancer cells.

Implementation Method 1

nucleic acid molecules comprising SEQ ID NO: 1 and nucleic acid molecules encoding the amino acid sequence set forth in SEQ ID NO:2

Methodology Applied
Scientific EffectGene expression:

Implementation Method 2

combined with adjuvants such as IL-12, IL-15, or RANTES, to enhance immunogenicity

Methodology Applied
Scientific EffectCytokine signaling:

Implementation Method 3

PRAME, originally identified as a gene encoding a HLA-A24 restricted antigenic peptide in human melanoma, triggers autologous cytotoxic T cell-medicated immune responses

Methodology Applied
Scientific EffectCytotoxic T cell-mediated immunity:

Data Source

PatentEP3737397B1Cancer vaccines targeting prame and uses thereof
Publication Date: 2022.11.30 INOVIO PHARMACEUTICALS INC
  • EP3737397B1 patent drawingFigure 1A~1B
  • EP3737397B1 patent drawingFigure 2
  • EP3737397B1 patent drawingFigure 3

AI summary

Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a mutated consensus PRAME antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a mutated consensus PRAME antigen are disclosed. Methods of treating a subject with a PRAME-expressing tumor and methods of preventing a PRAME-expressing tumor are disclosed. Mutated consensus PRAME antigen is disclosed.