Peptide Compounds for TA-MUC1 Cancer Detection
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Solution Overview
Problem
Current immunotherapeutic strategies for targeting MUC1 in cancer cells are limited by the immune system's inability to differentiate between tumor-associated MUC1 (TA-MUC1) and normal MUC1, leading to ineffective immune responses and potential autoimmune reactions, and existing compounds fail to specifically recognize TA-MUC1 for therapeutic and diagnostic applications.
Innovation Solution
Development of peptide-based compounds containing specific binding sites that selectively bind to TA-MUC1, identified through immunization with MUC1-derived glycopeptides, which are capable of distinguishing between TA-MUC1 and normal MUC1, allowing for targeted recognition and binding to tumor cells while sparing healthy cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapeutic strategies target MUC1 in cancer cells, then immune response is activated, but the immune system cannot differentiate between tumor-associated MUC1 and normal MUC1 leading to ineffective responses and potential autoimmune reactions
Solution Approach 1:
The patent applies local quality by targeting specific glycosylation patterns (Tn, STn, T antigens) that are locally present on tumor-associated MUC1 but absent or different on normal MUC1. The immunogenic composition is designed to recognize these specific local structural features rather than the entire MUC1 protein, enabling selective targeting of tumor cells while sparing healthy tissues.
Solution Approach 2:
The invention utilizes parameter changes in the glycosylation state of MUC1. Tumor-associated MUC1 exhibits aberrant glycosylation with short glycans and premature sialylation, creating distinct carbohydrate antigens. The patent exploits these parameter changes by designing immunogens that specifically recognize the altered glycosylation patterns on tumor cells, allowing the immune system to differentiate between normal and malignant cells based on these biochemical parameter differences.
2Measurement precision
If glycoproteins are used in immunotherapy to target TA-MUC1, then tumor targeting is achieved, but severe autoimmune reactions against normal MUC1 occur
Solution Approach 1:
The patent uses carbohydrate antigens (Tn, STn, T) as intermediaries that specifically bridge the immune system to tumor-associated MUC1. These glycan structures serve as mediators that are present on tumor cells but absent or different on normal cells, enabling the immune system to recognize and target tumors without reacting against healthy MUC1-expressing tissues. The glycan intermediaries provide the necessary specificity to avoid autoimmune reactions.
Solution Approach 2:
The invention exploits parameter changes in glycosylation patterns to achieve selective tumor targeting. The aberrant glycosylation of TA-MUC1 creates distinct carbohydrate structures that serve as specific markers. By designing immunogens that recognize these altered glycosylation parameters, the patent achieves high measurement precision in tumor recognition while avoiding cross-reactivity with normal MUC1, thus preventing autoimmune reactions.
3Measurement precision
If peptide-based compounds are designed to bind TA-MUC1, then specific tumor targeting is achieved, but the compounds must be chemically synthesized which increases complexity
Solution Approach 1:
The patent applies copying by creating simplified peptide-based models that replicate the key binding features of complex glycoproteins. Instead of using full-length glycosylated MUC1 proteins which require complex chemical synthesis, the invention uses shorter peptide sequences containing the essential binding motifs. These peptide copies maintain the ability to specifically bind TA-MUC1 while being much simpler to synthesize and produce, thus reducing manufacturing complexity while preserving binding specificity.
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 peptide-based compounds effectively differentiate between TA-MUC1 and normal MUC1, enabling specific targeting of tumor cells, reducing tumor size, and inducing a strong humoral immune response without autoimmune reactions, thus being suitable for the treatment, prevention, and diagnosis of cancers expressing TA-MUC1.
Implementation Method 1
novel compounds with the ability to bind to mammalian tumour-associated Mucin-1 (TA-MUC1) which can be found in MUC1-expressing tumour tissues
Implementation Method 2
inducing a strong humoral immune response without autoimmune reactions
Data Source
AI summary
The present invention relates to a compound comprising a first polypeptide sequence comprising at least three different amino acid sequences selected from the group consisting of GFTFSDYW (SEQ ID NO: 1), IRLKSNNYAA (SEQ ID NO: 2) and TFGNSFAY (SEQ ID NO: 3), a second polypeptide sequence comprising at least three different amino acid sequences selected from the group consisting of TGAVTTNNY (SEQ ID NO: 4), GTN (SEQ ID NO: 5) and ALWYSNHWV (SEQ ID NO: 6), or a variant of any one of said amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 6 having a different amino acid at one position, wherein said compound or variant is capable of binding to tumour-associated Mucin-1 (TA-MUC1).