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CD33 is a myeloid surface marker on the blasts of 85 to 90% of acute myeloid leukaemias and on normal myeloid cells, so drugs against it also hit healthy marrow. It is the target of gemtuzumab ozogamicin, the first ADC ever approved (2000), withdrawn in 2010 and re-approved in 2017 at a lower fractionated dose.
CD33 (Siglec-3) is a myeloid lineage marker expressed on the blasts of roughly 85 to 90 percent of acute myeloid leukaemias and on normal myeloid cells, so drugs against it hit healthy marrow as well as leukaemia. It is the antigen behind gemtuzumab ozogamicin, the first antibody-drug conjugate ever approved: approved in 2000, withdrawn in 2010 after toxicity and lack of confirmed benefit, and re-approved in 2017 at a lower fractionated dose. That history is an object lesson in ADC development, showing that dose schedule and linker stability can decide whether a valid target succeeds. Newer CD33 approaches, including bispecifics and CAR-T, still have to solve the same on-target myelosuppression. For a newcomer, CD33 is the AML surface marker on which the ADC field first learnt its lessons.
In plain words · CD33 is a myeloid surface marker on the blasts of 85 to 90% of acute myeloid leukaemias and on normal myeloid cells, so drugs against it also hit healthy marrow. It is the target of gemtuzumab ozogamicin, the first ADC ever approved (2000), withdrawn in 2010 and re-approved in 2017 at a lower fractionated dose.
CD33 is a myeloid surface marker on the blasts of 85 to 90% of acute myeloid leukaemias and on normal myeloid cells, so drugs against it also hit healthy marrow. It is the target of gemtuzumab ozogamicin, the first ADC ever approved (2000), withdrawn in 2010 and re-approved in 2017 at a lower fractionated dose.
Siglec-3; expressed on AML blasts and normal myeloid cells.
1 product aims at CD33: antibody-drug conjugates. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Lineage antigen shared with normal dendritic cells and monocytes and bone marrow cells and lymphoid tissue cells: the label readouts filed under it score its expression (CD33 expression (CD33-positive)), and HPA finds the gene group enriched in that blood lineage at or above 25 nTPM, so medicines aimed at it clear the normal lineage too. HPA CD33: RNA tissue enhanced (bone marrow 31 nTPM, lymphoid tissue 23 nTPM); blood lineage group enriched (dendritic cells 214 nTPM, monocytes 167 nTPM); high antibody staining in 1 normal tissue; highest cancer staining lymphoma (1 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); Open Targets associates it with 1 specific cancer type at or above 0.5 (acute myeloid leukemia). (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: CD33 expression (CD33-positive) label threshold; Human Protein Atlas CD33 tissue; Human Protein Atlas CD33 pathology; Open Targets ENSG00000105383 associations
First described 1988. Earliest sequence paper UniProt cites for the protein: Simmons et al, J. Immunol, 1988, "Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Siglec-3; expressed on AML blasts and normal myeloid cells.
RNA: tissue enhanced (bone marrow 31 nTPM, lymphoid tissue 23 nTPM), detected in many normal tissues. Blood: group enriched (dendritic cells 214 nTPM, monocytes 167 nTPM).
Medium: Epididymis, Kidney, Lymph node, Salivary gland, Spleen, Tonsil.
HPA CD33 tissue · HPA CD33 pathology · HPA protein class: CD markers, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Acute myeloid leukaemia | 85-90% | Blast surface expression | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Gemtuzumab ozogamicin (Mylotarg) is an anti-CD33 antibody linked to the DNA-cutting payload calicheamicin, the first ADC approved, in 2000 for relapsed acute myeloid leukaemia. An unstable linker and no benefit in a confirmatory trial led to withdrawal in 2010; it returned in 2017 at a lower fractionated dose, with liver toxicity, including veno-occlusive disease, its defining risk.
Query for this target: (TITLE:"CD33" OR ABSTRACT:"CD33") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CD33, not a curated reading list.
Shares Orum Therapeutics, Acute myeloid leukaemia, Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.