1x106 CAR T cells (figure 2). Conclusions These data suggest that LYL119, which combines c-Jun overexpression, NR4A3 KO, Epi-R protocol, and Stim-R technology, can limit exhaustion, maintain stem-like features, and has potential to provide effective and durable CAR T-cell antitumor activity in patients with ROR1+ solid tumors.

8 months ago

Preclinical • CAR T-Cell Therapy

EGFR (Epidermal growth factor receptor) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1) • IL2RA (Interleukin 2 receptor, alpha) • IL7R (Interleukin 7 Receptor) • NR4A3 (Nuclear receptor subfamily 4 group A member 3) • JUN (Jun proto-oncogene)

ROR1 expression • IL2RA expression • EGFR H1975 • IL7R expression

LYL119

1year

Preclinical Development of LYL119, a ROR1-Targeted CAR T-Cell Product Candidate Incorporating Four Novel T-Cell Reprogramming Technologies to Overcome Barriers to Effective Cell Therapy for Solid Tumors (ASGCT 2023)

Finally, we incorporated NR4A3 KO + c-Jun and Stim-R into the Epi-R protocol and showed that combining our four reprogramming technologies in ROR1 CAR T cells showed additive benefits to prolong in vitro cytotoxicity using A549 tumor cells compared to controls (Figure 1B). Together these data suggest that stacking these four technologies can limit exhaustion and has the potential to provide effective and durable ROR1 CAR T-cell functional activity in patients with ROR1+ solid tumor malignancies.

1 year ago

Preclinical • CAR T-Cell Therapy • IO biomarker

EGFR (Epidermal growth factor receptor) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1) • NR4A3 (Nuclear receptor subfamily 4 group A member 3) • JUN (Jun proto-oncogene)

EGFR H1975

LYL119