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**CD33-CPI dimer ADC** is a preclinical, site-specifically conjugated antibody-drug conjugate developed by Pfizer for acute myeloid leukemia. It comprises an anti-CD33 antibody bearing a heavy-chain Y296Q conjugation site and a cyclopropylindole payload dimer attached through an AcLysValCitPABC protease-cleavable linker. Following CD33 binding and internalization by myeloid leukemia cells, lysosomal linker processing releases the CPI dimer, a highly potent DNA-crosslinking cytotoxin. Although the platform showed strong preclinical activity and an improved therapeutic index relative to some earlier CD33 ADC approaches, the CD33-targeted construct caused severe hematologic toxicity in cynomolgus monkeys, consistent with CD33 expression on normal myeloid cells. ([europepmc.org](https://europepmc.org/article/MED/33148666))
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