Targeted cell selection and release using aptamer complexes in a cell processing system

Abstract

A cell processing platform and method for selective isolation and activation of target cells, such as T-cells, NK-cells, and hematopoietic stem cells, from a biological sample. The platform employs aptamer-functionalized microbubbles, which selectively bind to target cell surface antigens to create buoyant target cell-microbubble complexes. A centrifugation module separates buoyant target cells from non-target cells by exploiting their distinct buoyancy properties. The system includes advanced aptamer designs, such as Locked Nucleic Acid (LNA) modifications, temperature-controlled folding buffers, and reversible binding mechanisms using complementary strands or enzymatic cleavage to release target cells. Additional features include optimized spacer configurations to enhance binding accessibility and aptamer stability for high specificity and yield. This platform also enables selective removal of senescent cells using aptamer-functionalized microbubbles, facilitating continuous processing and supporting applications in cell therapy, research, and regenerative medicine.

Description

Attorney Docket No.473.10.PCT8 TARGETEDCELLSELECTION ANDRELEASEUSINGAPTAMERCOMPLEXES IN ACELLPROCESSING SYSTEM 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. 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Claims

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