Dual-BCMA CAR-T Cell Dosing for Relapsed Multiple Myeloma
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Solution Overview
Problem
Current therapies for multiple myeloma, including proteasome inhibitors and immunomodulatory drugs, often lead to relapse or refractoriness, necessitating the development of new treatment approaches.
Innovation Solution
Administration of chimeric antigen receptor (CAR)-modified T cells expressing an extracellular antigen binding domain targeting BCMA, a transmembrane domain, and an intracellular signaling domain, with specific dosing and administration methods tailored for optimal efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies) are used to treat multiple myeloma, then patient outcomes are improved, but patients will eventually relapse or become refractory to treatment
Solution Approach 1:
The patent changes the therapeutic parameter from conventional chemotherapy/immunomodulation to CAR-T cell therapy with dual BCMA targeting, fundamentally altering the mechanism of action to achieve sustained responses in relapsed/refractory patients
Solution Approach 2:
The CAR-T cell construct combines multiple functional elements: dual BCMA binding moieties (first and second binding domains), costimulatory domains, and signaling domains to create a composite therapeutic agent with enhanced persistence and efficacy
2Reliability
If CAR-T cell therapy is administered to treat multiple myeloma, then minimal residual disease reduction and clinical responses are achieved, but the complexity of the treatment increases
Solution Approach 1:
The CAR-T cell therapy process is segmented into distinct phases: cell collection, genetic modification with dual BCMA-targeting CAR, ex vivo expansion, quality control, and administration. This segmentation allows for standardized protocols and specialized facilities at each step
Solution Approach 2:
The patent introduces an intermediary ex vivo expansion step where CAR-T cells are genetically modified and expanded in controlled laboratory conditions before administration, serving as a bridge between cell collection and patient treatment
3Quantity of substance
If CAR-T cells are expanded in vitro prior to infusion, then the dose of CAR-T cells is increased, but the time required for treatment preparation is extended
Solution Approach 1:
The CAR-T cells undergo preliminary genetic modification and expansion in vitro before administration, allowing for optimization of cell dose and quality control measures to be performed in advance of patient treatment
Solution Approach 2:
The ex vivo expansion process is dynamically controlled with optimized culture conditions, cytokine concentrations, and expansion protocols to achieve maximum cell yield within the shortest possible timeframe
Data Source
AI summary
Provided herein is a method of treating a subject who has a cancer. At least one dose of chimeric antigen receptor (CAR)-T cells comprising a CAR comprising a polypeptide is administered to the subject. The peptide comprises an extracellular antigen binding domain with at least two BCMA-binding moieties, a transmembrane domain, and an intracellular signaling domain. The dose of CAR-T cells administered to the subject is from 4.0×105 to 1.0×106 of CAR-T cells per kilogram of the subject's mass. Alternatively, the dose comprises 1×106 to 1×108 of the CAR-T cells.