9:02 PM
Nov 29, 2018
 |  BC Innovations  |  Targets & Mechanisms

Souped-up CARs at ASH 2018

How modifications to CAR T and CAR NK cells stand to boost their function

Rather than searching for new antigens, makers of the latest generation of CAR therapies are focusing on the CARs themselves by designing more sophisticated methods of targeting multiple antigens, controlling cytotoxicity and enhancing tumor-homing.

BioCentury’s analysis of abstracts released ahead of this year’s American Society of Hematology (ASH) meeting finds 226 abstracts on CARs, about 40 of which describe new approaches for controlling CAR T cells or CAR NK cells in early development, from academic discovery to first-in-human trials.

A selection of the strategies is depicted below, with relevant abstract numbers shown for each (see “Figure: CAR Schematics”).

Figure: CAR schematics

Multispecific and universal CARs

At least three preclinical or first-in-human abstracts showcase CARs targeting multiple tumor antigens from a single construct, reducing the risk of tumor evasion and avoiding the need to test cocktails of singly targeted CAR T or CAR NK cells.

1) iCell Gene Therapeutics LLC has created a construct containing a CLEC12A-targeting CAR and a CD33-targeting CAR joined by a self-cleaving peptide that frees the two parts after translation. The approach streamlines production of the cell therapy by limiting the number of required transductions; it also ensures both CARs are expressed in equal numbers...

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