Novel Peptides for Tumor-Specific T-Cell Activation
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Solution Overview
Problem
Current immunotherapies for various cancers, such as glioblastoma, chronic lymphocytic leukemia, and non-small cell lung cancer, face challenges in eliciting effective anti-tumor immune responses due to limitations in identifying and targeting tumor-associated antigens, particularly those over-expressed in cancer cells but not in normal tissues, and in overcoming the immunosuppressive tumor microenvironment.
Innovation Solution
Development of novel peptide sequences derived from HLA class I molecules of human tumor cells that can bind to MHC molecules, inducing T-cell responses and serving as targets for antibodies and other binding molecules, combined with approaches to enhance peptide presentation and T-cell activation, to stimulate anti-tumor immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tumor-associated antigens are targeted for immunotherapy, then anti-tumor immune responses are elicited, but the complexity of identifying and selecting specific peptide epitopes increases
Solution Approach 1:
The patent segments the complex task of identifying tumor-associated antigens by focusing on specific peptide epitopes that are presented by MHC molecules. Instead of analyzing entire proteins or genomes, the invention isolates and sequences specific peptide fragments (typically 8-12 amino acids) that are processed and presented by tumor cells, thereby simplifying the identification process while maintaining immunotherapy effectiveness.
Solution Approach 2:
The invention extracts peptide epitopes from the complex proteomic landscape of tumor cells. By using mass spectrometry and other analytical techniques to identify and isolate specific peptide sequences that are over-expressed in tumors and presented by MHC molecules, the patent separates the relevant immunogenic elements from the background complexity of tumor protein expression.
2Reliability
If peptide sequences are designed to bind MHC molecules, then T-cell activation is enhanced, but the difficulty of predicting which peptides will elicit effective immune responses increases
Solution Approach 1:
The patent incorporates feedback mechanisms through pre-clinical and clinical testing to validate peptide selections. The results from these tests feed back into the design process, allowing iterative optimization of peptide sequences and presentation strategies. This feedback loop enables continuous improvement in predicting which peptides will elicit the most effective T-cell responses.
Solution Approach 2:
The invention replaces purely computational prediction methods with a combination of biochemical analysis and clinical validation. Instead of relying solely on algorithms to predict peptide-MHC binding and immune response, the patent uses experimental mass spectrometry to identify actual peptide presentations and clinical trials to measure immune responses, thereby improving prediction accuracy through empirical data.
3Reliability
If tumor cells are targeted specifically, then therapeutic efficacy is improved, but the challenge of overcoming the immunosuppressive tumor microenvironment increases
Solution Approach 1:
The patent uses dendritic cells as intermediary antigen-presenting cells that bridge the gap between tumor antigens and T-cells. These dendritic cells are loaded with tumor peptide epitopes and migrate to lymph nodes, where they present the peptides to naive T-cells, thereby mediating the initiation of anti-tumor immune responses while navigating the immunosuppressive tumor microenvironment.
Solution Approach 2:
The invention modifies the immunogenicity parameters of tumor antigens by selecting and presenting specific peptide epitopes that are optimized for T-cell recognition. By changing the presentation format from whole proteins to processed peptide fragments, and by selecting peptides with high immunogenicity scores, the patent enhances the ability to overcome immunosuppressive barriers in the tumor microenvironment.
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 novel peptide sequences and their variants, when used in vaccine compositions or as targets for immunotherapeutic agents, can potentially elicit robust anti-tumor immune responses, overcoming the limitations of current therapies by specifically targeting tumor cells while minimizing harm to normal tissues.
Implementation Method 1
The present invention relates to several novel peptide sequences and their variants derived from HLA class I molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses
Data Source
AI summary
A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC. A method of treating a patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC.