Isoform-Specific Binding Molecules for Cancer Targeting
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Solution Overview
Problem
Current cancer treatments, including traditional therapies and immunotherapies, face challenges in specificity and efficacy due to the limited differential expression of target antigens in cancerous tissues, leading to side effects and reduced quality of life, necessitating the development of more targeted and specific antibody-mediated approaches.
Innovation Solution
Development of binding molecules, such as antibodies and chimeric antigen receptors (CARs), that specifically target mesothelin isoforms and PD1 receptor molecules, with high affinity and specificity, to enhance cancer treatment efficacy by selectively binding to cancer cells and modulating immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional cancer therapies (chemotherapy, radiotherapy) are used, then curative effect is achieved in short term, but side effects increase and quality of life decreases
Solution Approach 1:
The patent segments the mesothelin protein into multiple isoforms (mesothelin-1, mesothelin-2, mesothelin-3) with distinct expression patterns. By developing binding molecules that specifically target cancer-expressed isoforms while sparing normal tissue-expressed isoforms, the treatment achieves cancer-specific efficacy while reducing off-target side effects.
Solution Approach 2:
The patent applies local quality by creating binding molecules with isoform-specific binding characteristics. Different binding molecules are designed to recognize specific mesothelin isoforms that are locally expressed in cancer tissues versus normal tissues, enabling selective targeting of cancer cells while preserving normal tissue function.
2Reliability
If traditional cancer therapies are used, then treatment is administered, but specificity for cancerous tissue is limited
Solution Approach 1:
The patent divides mesothelin expression into distinct isoform segments with different tissue distribution patterns. Mesothelin-1 is expressed in both normal and cancer tissues, while mesothelin-2 and mesothelin-3 are predominantly or exclusively expressed in cancer tissues. This segmentation enables the development of therapies with enhanced cancer tissue specificity.
Solution Approach 2:
The patent changes the binding specificity parameter of the binding molecules to recognize specific mesothelin isoforms. By adjusting the binding characteristics of antibodies or CARs to target cancer-specific isoforms (mesothelin-2, mesothelin-3) rather than all mesothelin variants, the treatment achieves higher cancer tissue specificity.
3Reliability
If immunotherapies with existing antigens are used, then immune response is activated, but differential expression of target antigen in cancerous tissue is limited
Solution Approach 1:
The patent segments the mesothelin antigen into multiple isoforms with differential expression patterns. By selecting isoforms that are specifically or preferentially expressed in cancer tissues (mesothelin-2, mesothelin-3) as targets for CAR-T cells or other immunotherapies, the treatment enhances antigen differential expression between cancerous and normal tissues, improving immune-mediated cancer cell killing while sparing normal tissues.
Data Source
AI summary
The technology relates in part to binding molecules that specifically bind to a polypeptide that is the Isoform 2 of mesothelin, or that specifically bind to an antigenic determinant (epitope) of the isoform 2 of mesothelin, or that specifically bind to polypeptides containing an antigenic determinant (epitope) of the isoform 2 of mesothelin, chimeric PD1 receptors that bind to PD ligands such as PDLs, to polynucleotides including vectors that encode such binding molecules, to ceils presenting such binding molecules and to methods of making such cells, to humanized forms of the binding molecules, and to methods of using such binding molecules, such as for treating cancers (e.g., ovarian cancers and mesotheliomas), including cancers in which the Isoform 2 of mesothelin is specifically expressed and/or upregulated relative to normal tissues.