Fig. 5: CDX0239-PBD demonstrates potent in vitro cytotoxicity in an ALK surface expression level-dependent manner in neuroblastoma cell lines. | Nature Communications

Fig. 5: CDX0239-PBD demonstrates potent in vitro cytotoxicity in an ALK surface expression level-dependent manner in neuroblastoma cell lines.

From: A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers

Fig. 5

A Structural representation of CDX0239-PBD with humanized anti-ALK antibody (CDX0239), linkers, cleavage site, and PBD payload. B Viability of NB-1, NB-SD, and SK-N-AS cell lines 5 days after treatment with CDX0239-PBD (red line with circles), free PBD (black line with triangles), and CDX0239 (blue line with squares) as compared to untreated controls quantified as percent relative light units (†P < 0.05, *P < 0.0001 vs free PBD treatment using a three-parameter log vs response analysis with n = 12 technical replicates for the CDX0239-PBD condition in all cell lines and the CDX0239 condition in NB-1 and NB-SD, and n = 9 technical replicates for the CDX0239 condition in SK-N-AS and for the free PBD condition in all cell lines). C Viability of NGP ALK wild-type (WT) 5 days after treatment with CDX0239-PBD (red line with circles) and free PBD (black line with triangles) and of NGP ALK knockout (KO) 5 days after treatment with CDX0239-PBD (peach line with circles) and free PBD (lavender line with triangles) as compared to untreated controls quantified as percent relative light units (†P < 0.05, *P < 0.0001 vs ALK WT CDX2039-PBD using a using a three-parameter log vs response analysis with n = 3 technical replicates per condition). D Caspase activity in NB-1, NB-SD, and SK-N-AS cell lines after treatment with CDX0239-PBD (red line with circles), free PBD (black line with triangles), and CDX0239 (blue line with squares) as compared to untreated controls quantified as percent relative light units (†P < 0.05, *P < 0.0001 vs free PBD treatment using a using a three-parameter log vs response analysis with n = 12 technical replicates for all conditions in NB-1 and NB-SD and n = 9 technical replicates for all conditions in SK-N-AS). E NB-1 cell line viability 5 days after treatment with 8 pM of CDX0239-PBD and increasing concentrations of co-treatment with CDX0239 as compared to controls treated with cell culture media only (vehicle) quantified as percent relative light units (†P < 0.05, *P < 0.0001 vs 0 pM CDX0239 using a two-away ANOVA analysis with Dunnett’s multiple comparison test with n = 12 technical replicates per condition). All data are plotted as mean ± standard deviation. Represented data has been validated with at least 3 independent experiments. Sample size, datasets, and exact p-values are located within the Source Data file. Source data are provided as a Source Data file.

Back to article page