Engineered B Cells With CD79a Signaling for Antitumor Therapy
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Solution Overview
Problem
Current cellular immunotherapies primarily focus on T cells, neglecting the potential of B cells, which play a crucial role in immune responses and have been associated with both hindered and improved cancer treatment outcomes, highlighting a need for alternative treatments beyond T cell therapies.
Innovation Solution
Engineered B cells with modified chimeric receptors (CAR-B cells) that incorporate CD79a for enhanced intracellular signaling, capable of expressing specific antigens or payloads, and administered with checkpoint inhibitors to target various diseases, including cancer, heart disease, and inflammatory conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If T cell therapies are used for cancer treatment, then antitumor response is improved, but treatment options are limited and B cell potential is overlooked
Solution Approach 1:
The invention segments the immune system focus from exclusive T cell therapy to include B cell therapy as a separate, viable approach. By developing CAR-B cells with specific signaling domains (CD79a, CD79b, CD40, CD19, CD137), the patent creates distinct therapeutic pathways that complement T cell therapies, thereby expanding treatment options while maintaining antitumor response effectiveness.
2Adaptability or versatility
If B cells are used for cancer treatment, then treatment versatility is improved, but intracellular signaling efficiency is insufficient
Solution Approach 1:
The patent applies parameter changes by systematically varying the intracellular signaling domain parameters in CAR-B cell constructs. Different signaling domains (CD79a with strong signaling, CD79b with weaker signaling, CD40, CD19, CD137) are tested to optimize B cell activation and antitumor response. This parameter optimization ensures that B cell therapies achieve sufficient intracellular signaling efficiency to be clinically effective.
3Adaptability or versatility
If B cells are used for cancer treatment, then alternative therapy is improved, but B cell role in antitumor response is unclear
Solution Approach 1:
The patent employs feedback mechanisms through preclinical models and clinical trial data that continuously refine understanding of B cell function in antitumor responses. By monitoring outcomes from CAR-B cell therapy and comparing them with established T cell therapy results, the invention builds evidence-based knowledge about B cell mechanisms, thereby reducing uncertainty about their therapeutic potential.
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 engineered B cells demonstrate superior efficacy in treating diseases by targeting specific cells, secreting therapeutic payloads, and modulating immune responses, offering a promising alternative to traditional T cell therapies.
Implementation Method 1
CD79 is comprised of two different chains known as CD79A and CD79B (also termed Igα and Igβ). Both CD79 chains contain an immunoreceptor tyrosine-based activation motif ('ITAM') in their intracellular tail regions that propagate a signal in a B cell.
Data Source
AI summary
The present invention relates to genetically modified B cells and their uses thereof, for example, for the treatment of a variety of diseases and disorders, including cancer, heart disease, inflammatory disease, muscle wasting disease, neurological disease, and the like. In certain embodiments, the invention relates to an isolated modified B cell (“CAR-B cell”), capable of expressing a chimeric receptor (“CAR-B receptor”), wherein said chimeric receptor comprises (a) an extracellular domain; (b) a transmembrane domain; and (c) a cytoplasmic domain that comprises at least one signaling domain. In various embodiments, the invention comprises an isolated modified B cell, wherein said B cell is capable of expressing and secreting a payload, wherein the payload is not naturally expressed in a B cell or is expressed at higher levels than is naturally expressed in a B cell. In various embodiments, the payload is an antibody or fragment thereof.