Compositions of enriched and modified cells

Abstract

The invention relates to a cell solution and composition optimized for selective isolation, genetic modification, and therapeutic use of target cells, such as T-cells, NK-cells, or hematopoietic stem cells. The solution comprises at least 90% target cells, with a minimum of 75% genetically modified cells, achieving high purity and viability rates through a functionally closed system. The method incorporates microbubble-based cell selection using lipid-shell microbubbles functionalized with antibodies or aptamers for high-affinity binding. The microbubbles enable buoyant separation under centrifugal force, with reversible binding mechanisms allowing for controlled cell release. The genetically modified cells exhibit functional transgene expression and retain therapeutic efficacy, including cytokine production upon activation. Additionally, the composition minimizes contaminants such as non-target cells or microbubble fragments, ensuring suitability for downstream therapeutic applications. This innovation supports high-efficiency, contamination-free cell processing for advanced immunotherapies and regenerative medicine.

Description

Attorney Docket No.473.10.PCT10 COMPOSITIONS OF ENRICHED AND MODIFIED CELLS Inventors: Jonathan Ellis and Philip H. Coelho Applicant: Trenchant BioSystems, Inc. RELATED APPLICATIONS

[0001] This application claims priority from the United States Provisional Application with Serial Number 63 / 616710 which was filed on December 31, 2023. The Provisional Application is hereby incorporated by reference in its entirety. TECHNICAL FIELD OF THE DISCLOSURE

[0002] This disclosure is generally related to cell therapies, and more particularly a device capable of separating target cells from non-target cells in blood or blood products and genetically modifying the target cells for clinical use in the field of cell and gene therapy. BACKGROUND

[0003] Gene-engineered autologous cell therapies, which utilize a patient’s own cells re- engineered and expanded ex vivo, represent a revolutionary approach to addressing complex diseases with high mortality and morbidity rates. These therapies leverage genetic modifications to correct underlying defects, offering transformative health outcomes for conditions where conventional treatments are limited or ineffective. Such gene-modified cell therapies, including those targeting hematopoietic cells such as T-cells, NK (Natural Killer) cells, and stem cells, have become a cornerstone of modern precision medicine, enabling targeted and durable interventions.

[0004] The field has witnessed rapid advancements, propelled by recent regulatory approvals and a robust development pipeline. Since 2017, multiple CAR-T cell therapies have received FDA approval for hematologic cancers, with over 1000 additional gene-modified therapies in U.S. clinical trials by late 2019. Beyond CAR-T therapies, CD34+ hematopoietic stem cells (HSCs) have shown similar promise for inherited disorders, including beta-thalassemia and severe combined immunodeficiency (SCID), with two therapies approved in the EU and over 31 pediatric trials underway in the U.S. as of 2019. Market forecasts predict a substantial expansion, with the global gene therapy market projected to grow from $18 billion in 2023 to over $97 billion by 2033. This growth reflects the increasing potential and demand for gene- modified cell therapies.

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Claims

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