Moving from autologous to allogeneic ACT paradigms
We have come so far in a relatively short time with Adoptive Cellular Transfer (ACT). The two marketed drugs in this space, Novartis’s Kymriah and Gilead/Kite’s Yescarta, are both CD19 CAR-T autologous constructs targeting lymphomas and Acute Lymphocytic Leukaemia (ALL).
These treatments are expensive and, at least in the US, subject to the FDA’s REMS programme limiting their use to certified healthcare facilities, owing to complex administration cell therapy guidelines from manufacturer as well as serious potential side effects such as cytokine release syndrome, macrophage activation syndrome and neurotoxicity. For autologous CAR-T products, manufacturing costs, logistics and hospital costs are very high, not least because of the management of patient chain of custody and the coordination of multiple institutional departments, such as the apheresis and transplant units, etc.
But things are changing rapidly with the advent of allogeneic approaches, whether they be cells derived from HLA typed and matched healthy donors (marrow or peripheral), or from gene edited donor cells which have been modified to allow them to be given to non-HLA matched patients or TAC-T cells (T-Cell antigen coupler). These approaches have the possibilities of therapies with potentially reduced safety concerns, a potentially higher therapeutic index, as well as breadth of targets including solid tumours.
Allogeneic CAR-T cells can be manufactured using T-Cells from just one, single healthy donor and can be used in multiple patients. Estimates from studies suggest that a single donor set may be sufficient to create therapeutic doses for over 200 average adult subjects.
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