Zhang Y, Tacheva-Grigorova SK, Sutton J, et al. Allogeneic CAR T Cells Targeting DLL3 Are Efficacious and Safe in Preclinical Models of Small Cell Lung Cancer. Clinical Cancer Research. 2023; (doi: 10.1158/1078-0432.CCR-22-2293).
New preclinical evidence suggests that aiming chimeric antigen receptor (CAR) T cells at delta-like ligand 3 (DLL3) may be a viable therapeutic pathway for small cell lung cancer (SCLC). DLL3 is a strong target for immunotherapy in this setting because while it is highly expressed on SCLC and other solid tumors, it is present only at low levels in healthy tissue. To explore, researchers implanted DLL3-expressing tumors in mice, which then received infusions of murine cross-reactive DLL3 CAR T cells. The investigators documented potent anti-tumor activity, including complete responses, in SCLC in vivo models. In vitro, a subset of CARs exhibited long-term killing potential. In addition to the favorable efficacy outcomes, the safety data showed no sign of pituitary or brain toxicity associated with DLL3 CAR T immunotherapy.