Self-driving CARs: Evolved, engineered vectors allow highly targeted, CRISPR-mediated in vivo engineering of CAR T-cells

Additionally, in vivogenerated CAR T-cells showed high rates of expansion after two weeks, followed by contraction after tumour clearance.

In designing and optimising this therapeutic strategy, researchers identified and addressed three common hurdles to development of in vivo CAR T therapies.

Characterisation of CAR T-cells revealed the following traits: Ki67 expression was found to be significantly increased, indicating a proliferative population; memory markers were maintained; regulatory T-cells were underrepresented in CAR T-cells; and ratios of helper to killer T-cells were balanced.

A recent review identifies examples of in vivo CAR T strategies currently in clinical and preclinical stages.

The major hurdle, therefore, is in establishing delivery vectors that are non-immunogenic and highly targeted to avoid deleterious off-target effects.