Multi-Supertype CTL Immunogens for Broad Cancer Immunity
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Solution Overview
Problem
Current cancer immunotherapy methods are limited in their ability to stimulate broad CTL responses across different HLA types, particularly for patients who do not express HLA-A2, and there is a need for identifying peptides that associate with other HLA molecules like HLA-A1, HLA-A24, and HLA-A3 supertypes, as well as peptides derived from multiple proteins to overcome tumor resistance mechanisms.
Innovation Solution
Development of immunogens comprising specific polypeptides with epitopic sequences that can induce CTL responses against various cancers, including ovarian, breast, pancreatic, and lung carcinomas, by utilizing nucleic acid molecules encoding these polypeptides and their full-length proteins, which can be administered as vaccines or used in vitro to generate CTLs for adoptive transfer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapy is designed to stimulate tumor-specific CTL response, then cancer control is improved, but the method is limited in its ability to stimulate broad CTL responses across different HLA types
Solution Approach 1:
The patent applies universality by designing immunogens that can elicit CTL responses across multiple HLA supertypes (HLA-A1, HLA-A2, HLA-A24, HLA-A3) rather than being limited to a single HLA type. The immunogens comprise polypeptides with epitopic sequences that are presented by multiple HLA molecules, enabling broad coverage across different patient populations and overcoming the limitation of HLA-type restricted immunotherapy.
2Reliability
If peptides are selected to associate with specific HLA molecules, then CTL recognition is improved, but the approach fails for patients who do not express those HLA molecules
Solution Approach 1:
The patent selects peptides that can be presented by multiple HLA supertypes, ensuring that the immunogen can elicit CTL responses in patients regardless of their specific HLA type. This multi-supertype approach ensures broad adaptability while maintaining reliable CTL recognition for each HLA type.
Solution Approach 2:
The patent changes the parameter of HLA type specificity by designing immunogens that target multiple HLA supertypes simultaneously. This parameter change from single-supertype to multi-supertype targeting enables the immunotherapy to adapt to different patient HLA profiles while maintaining effective CTL recognition.
3Ease of operation
If a single peptide is used as immunogen, then the immune response is focused, but tumor resistance mechanisms can overcome this limited approach
Solution Approach 1:
The patent applies segmentation by dividing the immunogen into multiple peptide components, each targeting different HLA supertypes or tumor antigens. This segmented approach ensures that if one peptide pathway is blocked by tumor resistance, other peptide components can still elicit effective CTL responses, thereby overcoming tumor resistance mechanisms while maintaining focused immune responses against specific tumor targets.
Solution Approach 2:
The patent uses composite immunogens that combine multiple polypeptides with different epitopic sequences capable of binding to multiple HLA supertypes. This composite structure provides both focused specificity against tumor antigens and broad coverage across HLA types, making the immune response more resilient to tumor resistance mechanisms.
Data Source
AI summary
The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of cancer, especially carcinomas, such as pancreatic carcinoma. The invention discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against pancreatic and other cancers.