Short hairpin RNA (shRNA) technology offers differentiated strategy to future development of CAR T
Celyad Oncology’s shRNA technology allows for the modulation of gene expression in our CAR T constructs without the need for gene-editing. We are currently engineering T-cells with specific desired features, including the inhibition of alloreactivity, increased persistence and enhanced antitumor activity or potentially improved tolerability. We have also validated the utility of our shRNA platform with our next-generation NKG2D receptor CAR T clinical candidate, CYAD-02, which incorporates a single shRNA hairpin targeting the NKG2D ligands MICA/MICB within the construct.
Our shRNA platform provides a versatile approach to the design and development of next-generation CAR T candidates with the potential to work with a broad array of CAR T constructs
Innovative technology built for allogeneic CAR T
Our CYAD-200 series of allogeneic CAR T candidates use shRNA to interfere with the expression of the TCR by knockdown of the RNA encoding the CD3ζ component of the TCR complex. Data from preclinical studies have shown shRNA knockdown targeting CD3ζ is as effective as gene-editing methods such as CRISPR/Cas9. In addition, preclinical data demonstrated expression of a single shRNA hairpin provides prolonged TCR knockdown.
The technology is also complementary to our All-in-One Vector approach, which allows for the expression of multiple shRNA hairpins in a single construct within a single transduction step. Data from preclinical studies demonstrate simultaneous knockdown of the multiple gene products at the mRNA and protein levels in a single multiplexed vector.
Celyad Oncology’s lead shRNA-based allogeneic CAR-T candidate, CYAD-211, which uses a single hairpin to knockdown the CD3ζ component of the TCR complex, is expected to enter the clinic by year-end 2020.