On February 18, 2025 Celyad Oncology (Euronext: CYAD) (the "Company"), reported the publication of the preclinical data of the non-gene edited allogeneic CYAD-211 and clinical data from the Phase I IMMUNICY-1 clinical study which evaluated CYAD-211 in relapsed or refractory (r/r) multiple myeloma (MM) patients (Press release, Celyad, FEB 18, 2025, View Source [SID1234650331]). The findings were published in the International Journal of Molecular Science (IJMS).
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CYAD-211 is the Company’s first allogeneic chimeric antigen receptor (CAR) T-cell candidate, engineered to co-express a B-cell maturation antigen (BCMA)-specific CAR and a microRNA-based single shRNA which interferes with the expression of the CD3ζ component of the T-cell receptor (TCR) complex, evaluated clinically.
The IJMS publication includes preclinical data which showcases the knockdown of CD3ζ efficiently removed the TCR complex from the cell surface, and inhibited TCR mediated activation in vitro and in vivo. The publication also presents clinical data of the dose-escalation segment of the IMMUNICY-1 phase-I clinical trial (NCT04613557) in patients with r/r MM. Importantly, data highlighted an overall good safety profile and some clinical responses, with no signs of graft-versus-host disease (GvHD), demonstrating the effectiveness and safeness of the technology to abrogate the risk of GvHD.
Overall, these data provides the proof-of-concept of the safe administration of CAR T-cells engineered using a miRNA-based shRNA technology. CYAD-211 is the first allogeneic CAR T-cell candidate using a non-gene edited approach to achieve allogenicity. This differentiated strategy provides key advantages by being easily implemented, safe, efficient, tunable, and with the possibility to modulate multiple target genes simultaneously.