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Home  >  Medical Research Archives  >  Issue 149  > Technological and Manufacturing Innovation Drive Improved Access to Engineered T Cell Therapies
Published in the Medical Research Archives
Nov 2023 Issue

Technological and Manufacturing Innovation Drive Improved Access to Engineered T Cell Therapies

Published on Nov 29, 2023




The creation of autologous gene-modified cell products, such as CAR-T cells (chimeric antigen receptor T cells) has met with clinical success but has been severely restricted by cost, availability, and current commercial models of central manufacturing. Moreover, the inability to produce CAR-T cells at reasonable cost in all but the largest centers slow innovation. CAR-T cells are unique in that these ex vivo expanded effector T cell populations express activation receptors comprised of immunoglobulin-like binders, or other immune ligands, bypassing the restriction of expanding and appropriately activating effector cells that arise by recombination of V-D-J genetic elements. However, the use of a single binding moiety to recognize leukemia target cells has selected for the generation of escape mutants, or for cryptic clones to expand that were not initially detected upon diagnostic work-up. To meet this challenge, we have engineered both B cell malignancy-specific and HIV surface antigen-specific CAR-T cells that express multiple binding moieties, thereby reducing the chance of immune escape. The creation of a therapeutic CAR-T cell population also requires a complex set of procedures that includes procurement of a large number of patient T cells, most often by leukapheresis, activation of the T cell population using matrix-associated antibodies targeting the T cell receptor and an immune co-receptor, a gene vector to permanently transduce T cells, and a bioreactor that can accommodate the expansion of the engineered cell population to numbers suitable for infusion. This complex set of procedures, combined with the current central processing model, has led to a complex chain of custody and expensive temperature-controlled shipping requirements. We present here a model whereby production of CAR-T cells at the point of care, using simplified cell procurement, purification, and expansion, can reduce the time and expense of CAR-T cell generation, with the aim to expand the use of these therapies in both the majority world, and in managed care or publicly funded systems. The CAR-T populations produced in this point-of-care ready process are highly active, viable, and have preferred CAR-T phenotypic characteristics associated with clinical efficacy.

Author info

Rimas Orentas, Ying Xiong, Yanping Xie, Zhongyu Zhu, Ibeawuchi Oparaocha, Oxana Sleesareva, Boro Dropulić

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