Fig 1: Anti-CCRL2 ADC shows higher cytotoxicity against MDS/AML cell lines compared to gemtuzumab and PBC-conjugated ADCs targeting CD33 and CD123.(A-C) Anti-CCRL2 ADC cytotoxicity against MOLM13, OCI-AML3 and MV4–11 cells derived from de novo/TP53-wild-type AML patients is relatively similar or lower compared to gemtuzumab and PBD-conjugated ADCs targeting CD33 and CD123. (D) Anti-CCRL2 ADC cytotoxicity against TF-1 cells (IC50 = 15.3 ng/ml) is higher compared to anti-CD123 (IC50 = 31.2 ng/ml), anti-CD33 (IC50 = 438.9 ng/ml) PBD-conjugated ADCs, gemtuzumab (IC50 = 296.5 ng/ml) or conjugated IgG2a (IC50 = 1159 ng/ml). (E) Anti-CCRL2 ADC cytotoxicity against F36P cells (IC50 =23.2 ng/ml) is higher compared to anti-CD123 (IC50 = 44.7 ng/ml), anti-CD33 (IC50 = 929.3 ng/ml) PBD-conjugated ADCs, gemtuzumab (IC50 = 1012.2 ng/ml) or conjugated IgG2a (IC50 = 1297.7 ng/ml). (F) Anti-CCRL2 ADC cytotoxicity against SKM1 cells (IC50 = 13.2 ng/ml) is higher compared to anti-CD123 (IC50 = 68.7 ng/ml), anti-CD33 (IC50 = 84.1 ng/ml) PBD-conjugated ADCs conjugated IgG2a (IC50 = 6455 ng/ml) and relatively lower compared to gemtuzumab (IC50 = 10.5 ng/ml). (G) The IC50 of anti-CCRL2 ADC is similar or higher compared to gemtuzumab and PBD-conjugated anti-CD33 and anti-CD123 ADCs in MOLM13, OCI-AML3 and MV4–11 cells but it is lower compared to gemtuzumab, PBD-conjugated anti-CD33 and anti-CD123 in TF-1 and F36P and compared to PBD-conjugated anti-CD33 and anti-CD123 in SKM1 cells. * p<0.010, ** p<0.001, Each experiment was repeated 3 individual times.