Peptide Vaccines Targeting AML Mutations for Immunotherapy
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Solution Overview
Problem
Current treatments for acute myelogenous leukemia (AML) have limited effectiveness, particularly for older patients, with low survival rates and significant side effects, and there is a need for more targeted and less toxic therapies to improve diagnosis, prognosis, and treatment outcomes.
Innovation Solution
Development of novel peptide sequences derived from HLA class I molecules of human tumor cells that can be used in vaccine compositions to stimulate anti-tumor immune responses, targeting specific T-cell epitopes to elicit immune responses against AML cells, and potentially other cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy treatments are used for AML, then some therapeutic effect is achieved, but survival rates remain low and side effects are significant
Solution Approach 1:
The invention segments the treatment approach by identifying and targeting specific peptide epitopes (such as those from NPM1, FLT3, IDH1, IDH2, and CEBPA mutations) that are uniquely expressed on AML cells. This allows the immune system to be directed against specific tumor-associated antigens rather than using non-specific chemotherapy, thereby improving treatment effectiveness while reducing harm to healthy cells.
Solution Approach 2:
The patent uses peptide vaccines as an intermediary to bridge the gap between the patient's immune system and AML cells. These peptides act as mediators that present tumor-specific antigens to T-cells, activating a targeted immune response against AML cells without requiring direct cytotoxic chemotherapy exposure, thus reducing side effects while maintaining therapeutic effectiveness.
2Productivity
If conventional chemotherapy is administered, then some cancer cells are killed, but treatment outcomes for older patients remain poor with limited effectiveness
Solution Approach 1:
The invention changes the fundamental parameter of treatment modality from non-specific chemotherapy to specific peptide-based immunotherapy. By identifying mutation-specific peptides (such as NPM1 mutated peptides, FLT3 ITD peptides, IDH1/IDH2 mutant peptides, and CEBPA mutated peptides), the treatment parameters are optimized to target AML cells with high specificity, improving both productivity (treatment outcome) and reliability (survival rate) particularly for older patients who respond poorly to conventional therapy.
3Reliability
If broad-spectrum chemotherapy is used, then some anti-cancer effect is achieved, but toxicity and harmful effects increase
Solution Approach 1:
The patent applies local quality by creating treatment specificity at the molecular level. Different peptide vaccines are designed for different AML subtypes based on their specific mutations (NPM1, FLT3, IDH1, IDH2, CEBPA, etc.). This localized, targeted approach ensures that the anti-cancer effect is concentrated on the specific tumor cells expressing those mutations, while healthy cells and non-mutated tumor cells are spared, thereby reducing toxicity while maintaining reliable anti-cancer effects.
Data Source
AI summary
The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.