Recombinant CD20 Feeder Cells for Antigen-Specific T-Cell Activation
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Solution Overview
Problem
Conventional chemotherapy and radiation treatments for lymphomas, such as B cell lymphoma, are non-targeted and non-specific, making them ineffective in addressing the disease effectively.
Innovation Solution
Development of recombinant CD20 antigen-presenting cells, including dendritic cells, macrophages, or B cells, transfected with nucleotide sequences encoding CD20 or its fragments, and further modified by gamma irradiation or heat killing, to create feeder cells that stimulate antigen-specific T cells, particularly CD8+ and CD4+ T cells, for targeted cancer cell destruction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional chemotherapy or radiation treatment is used, then treatment coverage is broad, but treatment specificity is poor and effectiveness is reduced
Solution Approach 1:
The therapy segments the broad treatment approach into specific components: isolating and activating specific T cell clones that recognize particular tumor antigens (such as CD20), thereby transforming non-specific chemotherapy into specific cellular therapy while maintaining the ability to target different tumor types through antigen selection
Solution Approach 2:
The patent uses antigen-presenting cells as intermediaries to bridge the gap between tumor antigens and T cell activation. These intermediary cells present processed tumor antigens to T cells, enabling specific recognition and activation without requiring direct contact between T cells and tumor cells, thus improving specificity while maintaining treatment effectiveness
2Reliability
If targeted cell therapy is developed, then treatment effectiveness is improved, but manufacturing complexity increases
Solution Approach 1:
The patent performs preliminary actions by pre-isolating and pre-activating T cells and antigen-presenting cells in controlled laboratory conditions before administration to the patient. T cells are activated in vitro using purified tumor antigens or antigen-presenting cells, and the activated cells are then frozen and administered later, simplifying the overall process by separating the complex activation step from the administration step
Solution Approach 2:
The patent utilizes parameter changes in cell activation states and antigen presentation to improve effectiveness. By controlling the activation parameters of T cells (such as co-stimulation signals, cytokine environment, and antigen concentration) and the presentation parameters of antigen-presenting cells, the therapy achieves high effectiveness while maintaining manageable manufacturing complexity through standardized protocol development
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 recombinant CD20 antigen-presenting cells enhance the specificity and efficacy of T cell therapies, enabling targeted killing of B cell lymphoma, T cell lymphoma, osteosarcoma, hemangiosarcoma, multiple myeloma, and plasma cell tumors by activating antigen-specific T cells.
Implementation Method 1
cells presenting a recombinant CD20 or fragment thereof... the recombinant CD20 or the fragment thereof comprises at least 80% sequence identity to SEQ ID NO: 1... the cell is an antigen presenting cell... the antigen presenting cell is a dendritic cell, a macrophage, or a B cell
Implementation Method 2
the cell is irradiated... the cell is exposed to a direct dose of gamma radiation... the cell line is at least 99%, at least 99.5%, or at least 99.9% inactivated
Implementation Method 3
the cell is heat killed... the cell is exposed to 57° C. for 25 minutes... the cell line is at least 99%, at least 99.5%, or at least 99.9% inactivated
Data Source
AI summary
The present disclosure provides compositions of immune cells presenting a target molecule or a fragment thereof and provides compositions and methods of producing immune cell therapies with targeted activity against cancer. Methods for conditioning a subject receiving the immune cell therapy of the disclosure are additionally disclosed. The immune cell therapies of the present disclosure can be administered to a subject in need thereof for diseases such as cancer.