Buoyancy-activated cell sorting (BACS)-compatible activation/transduction systems and methods

Abstract

Disclosed herein are methods for contacting in a closed container a host liquid including target cells, microbubble reagents comprising gas-core lipid-shelled microbubbles, and one or more antibodiesor other ligands that bind to cell surface molecules on the target cells, wherein the one or more antibodies or oilier ligands are bound to the target cells or the microbubbles, wherein the contactingunder conditions to produce target cells linked to microbubbles via the one or more antibodies or other ligands and activating the target cells to generate activated target cells.

Description

[0001] cross reference [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 643081, filed March 14, 2018, which is incorporated herein by reference in its entirety. Background technique [0003] Genetic modification of human lymphocytes is an increasingly important step in the development and manufacture of therapeutic living cell therapies such as chimeric antigen receptor T (CAR-T) cells. CAR-T cells, such as the first FDA-approved KYMRIAH (Tisagenlecleucel) for the treatment of acute lymphoblastic leukemia, are the patient's own (autologous) T lymphocytes prepared after a complex, expensive and time-consuming laboratory process. Kill cancer cells. [0004] Today, the manufacturing process of CAR-T cells typically involves the following sequential steps: (1) leukapheresis of the patient's blood to concentrate a large number of autologous leukocytes, followed by transport of the "leukapheresis product" from the outpatient clinic to the manu...

AI Technical Summary

Problems solved by technology

A distinguishing feature of these manufacturing processes from a commercialization standpoint is their complex, labor-intensive and inefficient nature, resulting in the extremely high cost of these life-saving therapeutics ($373,000 for a single dose course of Yescarta or KYMRIAH, respectively or $475,000)

With today's practice, the manufacturing paradigm typically involves dozens of sequential liquid handling steps and transfer of in-process materials to new containers (with associated cell loss), and, as cell isolation and cell washing steps would Additional cell loss results in relative inefficiency (low recovery of target cells), which in turn must pass through additional time for cell expansion (consumption of expensive cell culture medium and imposition of additional liquid handling steps, and Negative effect on the potential cell proliferation capacity in vivo) to compensate for the therapeutic dose

This complex production inefficiency and lengthy manufacturing process negatively impacts not only the cost of the product, but more importantly, the prognosis of critically ill patients as it impacts the timely manufacture of effective treatments, if available possibility of dosage

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