{"entity":{"id":"cd33","kind":"target","name":"CD33","aka":[],"tldr":"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 It is the target of gemtuzumab ozogamicin, the first ADC ever approved (2000), withdrawn in 2010 and re-approved in 2017 at a lower fractionated dose.","summary":"CD33 (Siglec-3) is a myeloid lineage marker expressed on the blasts of roughly 85 to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 It is the antigen behind gemtuzumab ozogamicin, the first antibody-drug conjugate ever approved: approved in 2000, withdrawn in 2010 after toxicity and lack of confirmed benefit, and re-approved in 2017 at a lower fractionated dose.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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD33","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD33"}],"tags":["adc-target"],"related":["cd33-expression"],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":["gemtuzumab-ozogamicin"],"companies":["actinium-pharmaceuticals","orum-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CD33","role":[],"sources":[],"specificity":"lineage-antigen","distribution":"one-type","specificityNote":"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.)","specificitySources":[{"label":"CD33 expression (CD33-positive) label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32fd2bb2-1cfa-4250-feb8-d7956c794e05","note":"CD33-positive"},{"label":"Human Protein Atlas CD33 tissue","url":"https://www.proteinatlas.org/ENSG00000105383-CD33/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas CD33 pathology","url":"https://www.proteinatlas.org/ENSG00000105383-CD33/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000105383 associations","url":"https://platform.opentargets.org/target/ENSG00000105383/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:1659","ensembl":"ENSG00000105383","uniprot":"P20138","entrez":"945","firstDescribed":1988,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3139766/","biology":"Siglec-3; expressed on AML blasts and normal myeloid cells.","whereFound":["Acute myeloid leukaemia"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"aml","pct":"85-90","measure":"Blast surface expression","source":"https://en.wikipedia.org/wiki/CD33"}]},"route":"/targets/cd33/","neighbours":{"biomarker":[{"id":"cd33-expression","kind":"biomarker","name":"CD33 expression (CD33-positive)","route":"/biomarkers/cd33-expression/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"}],"drug":[{"id":"gemtuzumab-ozogamicin","kind":"drug","name":"Gemtuzumab ozogamicin","route":"/drugs/gemtuzumab-ozogamicin/"}],"company":[{"id":"actinium-pharmaceuticals","kind":"company","name":"Actinium Pharmaceuticals","route":"/companies/actinium-pharmaceuticals/"},{"id":"orum-therapeutics","kind":"company","name":"Orum Therapeutics","route":"/companies/orum-therapeutics/"},{"id":"vor-biopharma","kind":"company","name":"Vor Biopharma","route":"/companies/vor-biopharma/"}],"trial":[{"id":"alfa-0701","kind":"trial","name":"ALFA-0701","route":"/trials/alfa-0701/"},{"id":"aaml0531","kind":"trial","name":"COG AAML0531","route":"/trials/aaml0531/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","route":"/technologies/radioimmunotherapy/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"}]}}