UBE2T Epitope Peptides for Specific CTL Induction
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Solution Overview
Problem
Current cancer vaccine trials using tumor-associated antigens (TAAs) have shown low objective response rates due to the immune system's recognition of TAAs as 'self', making it challenging to induce potent and specific anti-tumor immune responses.
Innovation Solution
Identification and use of specific epitope peptides derived from UBE2T, which are HLA-A24 or HLA-A2 restricted, to induce cytotoxic T lymphocytes (CTLs) that target cancer cells, including bladder, breast, and other types of cancer, by administering peptides or polynucleotides encoding these peptides to induce immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tumor-associated antigens (TAAs) are used as targets for immunotherapy, then anti-tumor immune responses can be induced, but the objective response rate remains low due to immune system recognition of TAAs as 'self'
Solution Approach 1:
The patent extracts specific epitope peptides from the UBE2T protein, isolating the immunogenic portions that can trigger T-cell responses. By using processed peptide epitopes rather than the full TAA protein, the invention reduces the 'self' recognition problem while maintaining anti-tumor activity. The peptides are selected and optimized to bind to HLA-A24 or HLA-A2 molecules, ensuring effective presentation to CD8+ CTLs.
Solution Approach 2:
The patent modifies the UBE2T protein by identifying and isolating specific epitope regions (amino acid sequences) that are most immunogenic. The peptide sequences are optimized for HLA binding affinity and T-cell recognition. This parameter optimization transforms the TAA into a effective vaccine antigen, improving response rates while minimizing immune escape.
2Reliability
If UBE2T-derived peptides are used to induce CTLs, then specific anti-tumor immune responses are achieved, but the complexity of peptide identification and selection increases
Solution Approach 1:
The patent segments the UBE2T protein into discrete epitope peptides of specific lengths (8-12 amino acids) that are optimally presented by HLA-A24 or HLA-A2. This segmentation allows systematic evaluation of individual peptide sequences for immunogenicity and HLA binding, simplifying the selection process while maintaining high specificity. The segmented approach enables parallel testing of multiple peptide candidates.
Solution Approach 2:
The patent uses HLA-A24 or HLA-A2 molecules as intermediaries between the UBE2T peptide and the CD8+ T-cell. This intermediary mechanism simplifies the overall system by providing a standardized presentation platform. The HLA molecule processes and presents the peptide epitope in a consistent manner, reducing the complexity of direct peptide-T-cell interactions.
3Adaptability or versatility
If peptide vaccination strategies are applied to various types of cancer, then new TAAs can be targeted, but the development time and clinical trial requirements extend the timeline
Solution Approach 1:
The patent identifies UBE2T as a universally expressed TAA across multiple cancer types (breast, ovarian, pancreatic, prostate, lung, colorectal, gastric, head and neck, bladder, cervical, and hematologic malignancies). This universality allows the same peptide vaccine platform to be applied across different cancer types, reducing development time. The peptide can be adapted for different HLA alleles (A24 or A2) to serve diverse patient populations.
Solution Approach 2:
The patent performs preliminary identification and characterization of UBE2T as a TAA with high expression in cancer cells and normal tissues. This preliminary work establishes the biological rationale and selects optimal epitope peptides before clinical trial initiation. The peptide sequences are pre-optimized for HLA binding and immunogenicity, accelerating the transition to clinical application.
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 UBE2T-derived peptides induce potent and specific immune responses against cancer cells, demonstrating CTL activity and potential for cancer immunotherapy, particularly in cancers with high UBE2T expression.
Implementation Method 1
CD8 positive cytotoxic T lymphocytes (CTLs) recognize epitope peptides derived from the tumor-associated antigens (TAAs) found on the major histocompatibility complex (MHC) class I molecule
Implementation Method 2
CTLs that target cancer cells, including bladder, breast, and other types of cancer
Data Source
AI summary
Peptide vaccines against cancer are described herein. In particular, epitope peptides derived from the UBE2T that CTLs are provided. Isolated antigen-presenting cells with CTL inducibility and CTLs that target such peptides, as well as methods for inducing the antigen-presenting cell, or CTL are also provided. The present invention further provides pharmaceutical compositions containing such epitope peptides derived from UBE2T or polynucleotides encoding the polypeptides as active ingredients. Furthermore, the present invention provides methods for the treatment and/or prophylaxis of (i.e., preventing) cancers (tumors), and/or the prevention of a postoperative recurrence thereof, as well as methods for inducing CTLs, methods for inducing anti-tumor immunity, using the epitope peptides derived from UBE2T, polynucleotides encoding the peptides, or antigen-presenting cells presenting the peptides, or the pharmaceutical compositions of the present invention.