DNAJB1-PRKACA Peptides for FL-HCC Immunotherapy
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Solution Overview
Problem
Current immunotherapies for cancer, particularly fibrolamellar hepatocellular carcinoma (FL-HCC), face challenges due to the lack of suitable tumor-associated T-cell peptide epitopes that can elicit specific immune responses, given the rarity and unique genetic characteristics of FL-HCC, which limits the broad applicability of existing treatments.
Innovation Solution
Development of peptides derived from the DNAJB1-PRKACA fusion transcript, specifically designed to bind to major histocompatibility complex (MHC) molecules and induce T-cell responses, including multifunctional CD8+ and CD4+ T cells, which are universally applicable across different MHC types, thereby targeting FL-HCC and other gastroenterological tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapies are used for FL-HCC, then general cancer treatment approaches are applied, but they fail to elicit specific immune responses due to lack of suitable tumor-associated T-cell peptide epitopes
Solution Approach 1:
The invention segments the DNAJB1-PRKACA fusion protein into specific peptide epitopes (e.g., SEQ ID NO: 1, SEQ ID NO: 5) that can be presented by MHC molecules. This segmentation allows the immune system to recognize specific tumor-associated antigens rather than requiring recognition of the entire fusion protein, thereby enabling specific immune responses against FL-HCC.
Solution Approach 2:
The identified peptide epitopes are designed to bind to multiple MHC class I and class II molecules across different human populations. This universality allows a single vaccine composition to potentially treat a broad range of patients regardless of their specific MHC genotype, enhancing the adaptability and broad applicability of the immunotherapy approach.
2Reliability
If FL-HCC is diagnosed early, then treatment outcomes improve, but the disease is often advanced when diagnosed due to lack of symptoms
Solution Approach 1:
The vaccine composition is designed for prophylactic and therapeutic use, aiming to stimulate anti-tumor immune responses before the disease progresses to advanced stages. By establishing specific immune responses early through vaccination with DNAJB1-PRKACA-derived peptides, the treatment seeks to prevent or delay the loss of time associated with late diagnosis.
3Reliability
If peptides are designed to bind to specific MHC molecules, then T-cell responses are induced, but the rarity and unique genetic characteristics of FL-HCC limit broad applicability
Solution Approach 1:
The vaccine composition incorporates peptide epitopes that are predicted to bind to multiple MHC class I and class II molecules with different alleles. This multi-functional design allows the same vaccine formulation to potentially induce T-cell responses across diverse patient populations, overcoming the limitation of FL-HCC rarity and unique genetic characteristics while maintaining specific immune responses.
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 peptides induce persistent and relapse-free T-cell responses in FL-HCC patients, demonstrating their potential as effective active agents in vaccine compositions for the treatment and prophylaxis of FL-HCC and other cancers with the DNAJB1-PRKACA fusion.
Implementation Method 1
peptides derived from the DNAJB1-PRKACA fusion transcript, specifically designed to bind to major histocompatibility complex (MHC) molecules and induce T-cell responses
Data Source
AI summary
The present invention relates to peptides, antigen binding proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer, especially of fibrolamellar hepatocellular carcinoma (FL-HCC). The present invention furthermore relates to tumor-associated T-cell peptide epitopes and recombinant T-cell receptors 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.