Journal: Clinical Cancer Research

Article Title: The Pharmacologic Profile of ART6043, a First-in-Class Clinical DNA Polymerase Theta Polymerase Domain Inhibitor Potentiating PARP Inhibitor Efficacy

doi: 10.1158/1078-0432.CCR-26-0493

Figure Lengend Snippet: ART6043 potentiates PARP inhibition in vitro . A, Representative CTG assay combination matrix for DLD-1 BRCA2 −/− (left) and DLD-1 wild-type (right) cells treated with titrated ART6043 and talazoparib for 14 days. Intensity of blue color indicates the level of synergy. % Control indicates relative viability. B, Representative IncuCyte growth curves for DLD-1 BRCA2 −/− cells treated with ART6043 or talazoparib as monotherapy or in combination at the indicated doses for 14 days. C, As for A but using olaparib instead of talazoparib. D, As for B but using olaparib instead of talazoparib. ART6043 concentrations represent free drug in tissue culture medium.

Article Snippet: Cells were imaged on the IncuCyte Live-Cell Imaging System (Essen Biosciences, RRID:SCR_023147).

Techniques: Inhibition, In Vitro, CTG Assay, Control, Tissue

Journal: Clinical Cancer Research

Article Title: Preclinical Characterization of CLSP-1025, a First-in-Class, Mutation-Specific T-Cell Engager Targeting a Neoantigen Derived from a Common p53 Mutation

doi: 10.1158/1078-0432.CCR-26-1252

Figure Lengend Snippet: CLSP-1025 demonstrates functional activity in various cellular systems including cell cocultures and patient-derived organoids. A, CLSP-1025–mediated cytotoxicity in cocultures of PBMCs and HLA-A*02:01 + –p53 R175H+ tumor cells. Cytotoxicity is reported as the percent tumor-cell death after a 96-hour coculture (mean ± SEM; n = 2). B, HLA-A*02:01 surface expression on p53 R175H+ TYK-nu cells after 72 hours of IFN-γ treatment, measured by geometric mean fluorescence intensity (gMFI) via flow cytometry. Data shown as mean; n = 3 technical replicates. C, CLSP-1025–mediated cytotoxicity in PBMC cocultures with TYK-nu cells with or without IFN-γ pretreatment, shown as percent tumor-cell death (mean ± SEM; n = 3 technical replicates). D–E, CLSP-1025–mediated cytotoxicity and IFN-γ secretion in PBMC cocultures with HLA-A*02:01 + –p53 R175H + adenocarcinoma organoids, measured by percent tumor-cell death and MSD, respectively [mean ± standard deviation (SD); n = 1 PBMC donor and technical duplicates for IFN-γ measurements]. F and G, CLSP-1025–mediated cytotoxicity and IFN-γ secretion in PBMC cocultures with HLA-A*02:01 + –p53 WT adenocarcinoma organoids. H, CLSP-1025–mediated killing of GFP + KLE cells when cocultured with isolated CD4 + , CD8 + , or bulk CD3 + T cells. GFP signal was quantified in real time using Incucyte and plotted as normalized fluorescence units [GFP fluorescence units (GFU) × μm 2 /image]. Data shown as mean ± SD; n = 2 technical replicates.

Article Snippet: The plates were incubated in an Incucyte S3 imager (Sartorius: Incucyte S3 live-cell analysis system, RRID: SCR_023147) for 160 hours and whole-well images captured every 4 hours.

Techniques: Functional Assay, Activity Assay, Patient-Derived Organoids, Expressing, Fluorescence, Flow Cytometry, Organoids, Standard Deviation, Isolation