AntiCD33

AntiCD33 refers to therapeutic approaches that target the CD33 antigen, a sialic acid–binding immunoglobulin-like lectin expressed on most myeloid cells, including many acute myeloid leukemia (AML) blasts, as well as on normal monocytes and granulocytes. Because CD33 is broadly present on malignant myeloid cells but not on hematopoietic stem cells, it has been explored as a means to selectively deliver cytotoxic effects to leukemic cells while attempting to preserve other tissues. Therapeutic strategies include naked monoclonal antibodies against CD33, antibody–drug conjugates (ADCs) that release a toxin after internalization, and bispecific T-cell engagers that recruit T cells to CD33-expressing targets. On-target, off-tumor toxicity to normal myeloid cells and associated cytopenias are important considerations in development and clinical use.

Gemtuzumab ozogamicin (GO, Mylotarg) is a prominent anti-CD33 ADC in clinical history. It consists of an anti-CD33 antibody linked to the cytotoxic agent calicheamicin. GO was approved for AML in 2000, withdrawn in 2010 due to safety concerns and overall survival signals, and reintroduced in 2017 at a lower dose with restricted indications in several regions. Other anti-CD33 programs have included lintuzumab, a naked anti-CD33 monoclonal antibody, and vadastuximab talirine (SGN-CD33A), an ADC. Development of vadastuximab talirine was halted after unfavorable safety outcomes in late-stage trials, and the program was not continued.

In summary, antiCD33 encompasses a range of strategies aimed at exploiting CD33 as a therapeutic target in AML and related myeloid disorders, with mixed clinical success and ongoing evaluation of safety, dosing, and patient selection.