Neo-epitope Identification via MHC Conformational Stability
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Solution Overview
Problem
Current cancer therapies, such as chemotherapy, lack specificity and often attack normal tissues, leading to side effects and limited efficacy. There is a need for methods to determine cancer specificity and develop non-toxic, effective therapies.
Innovation Solution
A method is described for identifying immunologically protective neo-epitopes in cancer patients by providing a putative neo-epitope set, determining the conformational stability of these epitopes bound to MHC proteins, and selecting epitopes with higher stability compared to their wild-type counterparts. These selected epitopes are then used to create pharmaceutical compositions for immunotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemotherapy is used to treat cancer, then cancer cells are attacked, but normal tissues are also attacked causing side effects
Solution Approach 1:
The patent segments the cancer treatment approach by identifying and targeting specific neo-epitopes that are unique to cancer cells. Instead of using broad-spectrum chemotherapy that affects all rapidly dividing cells, the invention divides the problem into identifying tumor-specific antigens and creating targeted immunotherapies against those specific targets, thereby sparing normal tissues from damage
Solution Approach 2:
The patent applies local quality by creating immunotherapies with high specificity for cancer cells through neo-epitope targeting. The immune response is locally directed at cancer-specific antigens rather than having systemic effects on all cells. The conformational stability assessment ensures that only epitopes with appropriate binding characteristics are selected, creating a targeted approach that concentrates therapeutic effect on cancer cells while minimizing impact on normal tissues
2Adaptability or versatility
If conventional cancer therapies are used, then treatment coverage is broad, but specificity to cancer cells is low
Solution Approach 1:
The patent applies preliminary action by conducting extensive in silico screening and conformational stability assessment of neo-epitopes before clinical application. The methodology pre-identifies and validates tumor-specific epitopes through computational modeling of MHC binding stability, ensuring high specificity is achieved before the therapy is administered to patients
Solution Approach 2:
The patent utilizes parameter changes by assessing conformational stability as a key parameter for epitope selection. By evaluating the stability of peptide-MHC complexes through computational methods, the invention selects epitopes with optimal binding characteristics, transforming the selection process from empirical to parameter-driven, thereby achieving both broad applicability and high specificity
Data Source
AI summary
Described herein are methods of identifying immunologically protective neo-epitopes from the cancer tissue DNA of cancer patients using biophysical principles as well as bioinformatics techniques. The identification of immunologically protective neo-epitopes provides pharmaceutical compositions with a limited number of tumor-specific peptides suitable for personalized genomics-driven immunotherapy of human cancer. Specifically disclosed herein is a method of using the conformational stability of an epitope in an MHC protein-binding groove to predict immunogenicity of peptides in a putative neo-peptide set from a tumor from a cancer patient. Pharmaceutical compositions and methods of administration are also included.