Table 1.
Relationship between MEDI-565 directed cytotoxicity of cancer cell lines and their mutational status and CEA density. Results from various cytotoxicity assays are shown. Potency of redirected T cell lysis of human cancer cell lines is reported as EC50 values in ng/mL. Each assay used an unique set of donor T cells, an E:T ratio of 5:1 and an assay duration of 48 hours. Cytotoxicity measurements for ASPC1, MKN45 and PC3 cell assays utilized a flow cytometry-based readout; for LS174T, HT-29, BXPC3, PAN0813, HPAFII, HPAC, H727, A549 and BT474 cell assays a caspase 3 measurement was used. Somatic mutation status for the indicated genes for each cell line was compiled from the COSMIC database (http://www.sanger.ac.uk/cosmic). N, number of replicate lysis experiments; EC50, antibody concentration required for half-maximal effective cell lysis; CEA density, MEDI-565 binding sites per cell; ND, not determined
| Mutational Status |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cell Line | Tissue Origin | Kras | BRAF | PTEN | PI3KCA | TP53 | N | Potency of Redirected Lysis EC50 (ng/mL) | CEA Density |
| HT-29 | Colon | Q61L | V600E | WT | P449T | R273H | 2 | 58 ± 10 | 9,700 |
| LS174T | Colon | G12D | WT | WT | H1047R | WT | 6 | 5.1 ± 3.7 | 75,000 |
| ASPC-1 | Pancreas | G12D | WT | WT | WT | C135Fs*35 | 14 | 3.5 ± 4.5 | 460,000 |
| BXPC3 | Pancreas | WT | WT | WT | WT | Y220C | 5 | 4.3 ± 2.7 | 200,000 |
| HPAC | Pancreas | G12D | WT | WT | WT | WT | 7 | 79 ± 62 | 1,400,000 |
| HPAFII | Pancreas | G12D | WT | WT | WT | P151S | 6 | 220 ± 170 | 810,000 |
| PAN0813 | Pancreas | G12D | WT | WT | WT | WT | 2 | 21 ± 16 | ND |
| MKN45 | Gastric | WT | WT | WT | WT | WT | 4 | 29 ± 20 | 370,000 |
| A549 | Lung | G12S | WT | WT | WT | WT | 3 | 66 ± 72 | ND |
| H727 | Lung | G12V | WT | WT | WT | Q165_166insYKQ | 5 | 77 ± 55 | 530,000 |
| BT474 | Breast | WT | WT | WT | K111N | E285K | 3 | 3.7 ± 2.3 | ND |
| PC3 | Prostate | GV12 | WT | R55Fs*1 | WT | K139fs*31 | 2 | 43 ± 7.1 | ND |