Disulfide-Crosslinked Polymeric Carrier for Th1 Immune Response
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Solution Overview
Problem
Current lymphoma vaccines face challenges in inducing an effective Th1-shifted immune response due to the use of self-antigens with low immunogenicity and the need for adjuvants that can overcome immune tolerance and enhance antigen-specific immune responses, while existing adjuvants like KLH and GM-CSF have limitations such as reactogenicity and inducing Th2-type immunity.
Innovation Solution
A pharmaceutical composition comprising a polymeric carrier cargo complex formed by disulfide-crosslinked cationic components and nucleic acids, associated with idiotype immunoglobulins or T cell receptors, to induce an adaptive immune response and support a Th1-shifted immune response, potentially using nucleic acid-based adjuvants like CpG or IFN-alpha to enhance immune activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If self-antigens are used for lymphoma vaccination, then the vaccine is specific to the tumor, but the immunogenicity is low and immune tolerance develops
Solution Approach 1:
The patent combines self-antigens (idiotype immunoglobulins or T cell receptors) with adjuvants (CpG oligonucleotides or IFN-alpha) to create a composite vaccine formulation. This composite approach maintains the tumor-specificity of the self-antigen while adding the immunostimulatory properties of the adjuvant to overcome low immunogenicity and break immune tolerance
Solution Approach 2:
The patent introduces adjuvants as intermediary substances that mediate between the self-antigen and the immune system. These adjuvants act as bridges that enhance the recognition and response to self-antigens, which normally would be tolerated by the immune system, thereby enabling effective anti-tumor immunity
2Reliability
If adjuvants like KLH are used to enhance immunogenicity, then the immune response is boosted, but reactogenicity and Th2-type immunity are induced
Solution Approach 1:
The patent changes the type and properties of adjuvants used in lymphoma vaccines, transitioning from protein-based adjuvants like KLH to nucleic acid-based adjuvants like CpG oligonucleotides or IFN-alpha. This parameter change in adjuvant chemistry enables Th1-type immune responses while reducing reactogenicity compared to traditional adjuvants
3Reliability
If high antigen doses are administered to overcome low immunogenicity, then the immune response is enhanced, but side effects increase
Solution Approach 1:
The patent uses adjuvants as intermediaries that amplify the immune response to low doses of self-antigens. This allows achieving effective immunogenicity with minimal antigen doses, thereby avoiding the side effects associated with high antigen dosing while maintaining strong tumor-specific immune responses
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 composition efficiently induces a Th1-shifted immune response, promoting potent and persistent immune responses against lymphoma, reducing the need for high antigen doses and minimizing side effects, with improved stability and delivery of nucleic acids in vivo.
Implementation Method 1
a polymeric carrier formed by disulfide-crosslinked cationic components as a carrier
Data Source
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Figure 3A~3B
AI summary
The present invention is directed to a pharmaceutical composition including (eg for use as an adjuvant) a polymeric carrier cargo complex, comprising as a carrier a polymeric carrier formed by disulfide-crosslinked cationic components and as a cargo at least one nucleic acid (molecule) and at least one antigen associated with a tumour or cancer disease selected from; an idiotype immunoglobulin (e.g. an idiotype antibody or an idiotype B cell receptor); or at least one idiotype T cell receptor, or in each case a fragment, variant and/or derivative thereof. The inventive pharmaceutical composition allows for efficient induction of an adaptive immune response directed against the idiotype immunoglobulin or T cell receptor, particularly of a Th1-shiftet immune response. The present invention furthermore provides kits or kits of parts comprising the components of the inventive pharmaceutical composition, as well as the use of the inventive pharmaceutical composition or the inventive kit as a vaccine, particularly in the therapy of a tumour or cancer disease such as lymphoma, particularly B cell or T cell lymphoma.