Table 2.
The selectivity of IL3RA-ADC compared to the isotype control ADC.
| Cytotoxicity, IC50 (M) | ||||||
|---|---|---|---|---|---|---|
| Compound | DAR | MV-4-11 (IL3RA ≈26,700) |
MOLM-13 (IL3RA ≈15,100) |
HDLM-2 (IL3RA ≈74,300) |
THP-1 (IL3RA ≈21,100) |
NCI-H292 (IL3RA ≈500) |
| IL3RA-ADC | 6.3 | 1.58 × 10−10 | 6.37 × 10−10 | 1.29 × 10−9 | 2.92 × 10−9 | >3.00 × 10−7 |
| Control ADC | 7 | >3.00 × 10−7 | 2.18 × 10−9 | 1.52 × 10−7 | 1.48 × 10−8 | 2.12 × 10−7 |
| IL3RA-Ab | n.a. | >3.00 × 10−7 | >3.00 × 10−7 | >3.00 × 10−7 | >3.00 × 10−7 | >3.00 × 10−7 |
| KSPi SMOL | n.a. | 9.05 × 10−11 | 8.95 × 10−11 | 1.00 × 10−10 | 3.07 × 10−10 | 2.16 × 10−10 |
In vitro cytotoxicity (CellTiter-Glo®, Promega) of the IL3RA-ADC BAY-943, isotype control ADC BAY-229, IL3RA antibody TPP-9476, and small molecule KSP inhibitor BAY-331 in the IL3RA-positive AML cell lines MV-4-11, MOLM-13, HDLM-2, THP-1 and in the IL3RA-low expressing NSCLC cell line NCI-H292 after 72 h incubation time. Anti-IL3RA ABC levels as determined by quantitative flow cytometry are indicated in the parentheses after each cell line. Ab, antibody; ADC, antibody–drug conjugate; DAR, drug-to-antibody ratio; n.a., not applicable; NSCLC, non-small-cell lung carcinoma; SMOL, small molecule.