FOXM1 Peptide HLA-A2 Binding for Killer T Cell Activation
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Solution Overview
Problem
Current therapeutic methods for biliary tract cancer, lung cancer, and pancreatic cancer, such as surgical therapy, chemotherapy, and radiotherapy, are often ineffective, especially for metastatic or intractable cases, highlighting the need for novel immunotherapy approaches that can enhance anti-cancer immunity without adverse events.
Innovation Solution
Identification and use of FOXM1 peptides, specifically those with an HLA-A2 binding motif, to induce killer T cells that recognize and target cancer cells expressing FOXM1, thereby activating an immune response against these cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If surgical therapy, chemotherapy, and radiotherapy are used for biliary tract cancer, lung cancer, and pancreatic cancer, then treatment can be provided, but therapeutic effectiveness is poor especially for metastatic or intractable cases
Solution Approach 1:
The patent changes the therapeutic approach from conventional surgery/chemotherapy/radiotherapy to immunotherapy by modifying the treatment parameter from direct tumor destruction to immune system activation. The FOXM1 peptide vaccine induces specific cytotoxic T cells that recognize and attack cancer cells expressing FOXM1, fundamentally changing the mechanism of action to achieve better therapeutic effectiveness particularly for metastatic cases
Solution Approach 2:
The patent introduces FOXM1 peptides as an intermediary substance that mediates between the immune system and cancer cells. The peptides bind to HLA-A2 molecules on antigen-presenting cells, serving as a bridge to activate cytotoxic T cells that then target and destroy FOXM1-expressing cancer cells, providing a novel therapeutic pathway ineffective conventional treatments cannot achieve
2Ease of operation
If conventional therapies are applied to metastatic or intractable cancer cases, then treatment can be administered, but adverse events occur and therapeutic effects are limited
Solution Approach 1:
The patent extracts the FOXM1 antigen specifically from cancer cells and uses it as a targeted vaccine. By isolating and utilizing only the cancer-specific FOXM1 peptide that binds to HLA-A2, the treatment achieves high specificity for cancer cells while sparing normal cells, thereby reducing adverse events associated with conventional systemic therapies that affect both cancer and healthy tissues
Solution Approach 2:
The patent applies local quality by targeting therapy specifically at FOXM1-expressing cancer cells through HLA-A2 restricted peptide presentation. The immunotherapy mechanism is localized to cells that express both FOXM1 and HLA-A2, allowing treatment to be administered broadly while the actual therapeutic effect is concentrated specifically at the cancer cell level, minimizing harm to normal cells
3Reliability
If FOXM1 peptides with HLA-A2 binding motif are used to induce killer T cells, then specific cytotoxic activity against cancer cells is achieved, but the approach is limited to HLA-A2 positive patients
Solution Approach 1:
The patent changes the HLA restriction parameter by selecting FOXM1 peptides with specific binding motifs for HLA-A2, the most common HLA allele in the Japanese population. This parameter optimization ensures high-affinity binding and effective immune activation, achieving reliable specific cytotoxic activity against cancer cells while maintaining broad applicability to approximately 30% of Japanese cancer patients who are HLA-A2 positive
Data Source
AI summary
An objective of the present invention is to provide a means for enabling cancer immunotherapy that targets approximately 30% of various cancer patients that highly express forkhead box M1 (FOXM1) among the Japanese, by identifying FOXM1-derived peptides that can activate cancer cell-damaging human killer T cells by binding to HLA-A2. The present invention provides a peptide of (A) or (B) below:(A) a peptide including the amino acid sequence of any one of SEQ ID NOs: 1 to 3;(B) a peptide which includes the amino acid sequence of any one of SEQ ID NOs: 1 to 3,wherein one, two, or several amino acid(s) are substituted, deleted, inserted, and/or added, andwherein the peptide shows cytotoxic (killer) T cell-inducing activity.