{"entity":{"id":"cd38","kind":"target","name":"CD38","aka":[],"tldr":"CD38 is a myeloma surface enzyme and the target of daratumumab, which is now given as a quick under-the-skin injection.","summary":"CD38 is an ectoenzyme (an NADase) present on the surface of more than 95 percent of myeloma plasma cells and on a variable 60 to 80 percent of AML blasts. Antibodies against it kill myeloma cells through complement, antibody-dependent cytotoxicity and phagocytosis, and add an immunomodulatory effect by depleting CD38-positive regulatory cells. The CD38 antibodies daratumumab and isatuximab are backbone myeloma therapy from first line onward, and subcutaneous formulations (Darzalex Faspro, Sarclisa Escena) dominate because they replace long infusions with a quick injection. Open issues include CD38 downregulation after exposure, interference with blood-typing and flow-cytometry assays, and the best way to sequence CD38 antibodies with T-cell-redirecting therapies. In short, CD38 is the surface enzyme that made antibody therapy a standard part of myeloma care.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD38","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD38"},{"label":"Kataoka et al., Nat Genet 2015: integrated molecular analysis of 426 adult T-cell leukaemia/lymphoma cases","url":"https://doi.org/10.1038/ng.3415"}],"tags":["antibody-target"],"related":["cd38-expression"],"cancers":["multiple-myeloma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["sg301","sti-6129"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Lymphoma: Plasma cells and plasmablastic tumours, and a minority of T-cell and NK-cell lymphomas. In lymphoma it is a research target, not a standard one. Also on healthy cells: Plasma cells, activated lymphocytes, NK cells, and at lower levels B and T cells and myeloid cells; the Human Protein Atlas reads CD38 as group enriched across B cells, NK cells and dendritic cells. What the medicine does: CD38 is an ectoenzyme rather than a receptor, and the licensed antibodies (daratumumab, isatuximab) work through complement, antibody-dependent cytotoxicity and phagocytosis plus depletion of CD38-positive regulatory cells. There is no approved anti-CD38 indication in lymphoma; the plasmablastic and NK/T-cell settings are case series and small trials. How tumours lose it: Surface CD38 falls under anti-CD38 antibody pressure, which is the documented mechanism in myeloma and the reason retreatment works poorly. What that costs the patient: Infusion reactions, and a laboratory problem that matters in practice: anti-CD38 antibodies bind CD38 on red cells and cause a positive indirect antiglobulin test that masks alloantibodies, so the transfusion laboratory must be told before a crossmatch."],"symbol":"CD38","role":[],"sources":[],"specificity":"lineage-antigen","distribution":"few-types","specificityNote":"Lineage antigen shared with normal lymphoid tissue cells: HPA blood lineage group enriched at or above 25 nTPM, and 2 cell-killing or cell-finding medicines (STI-6129, ISB 2001) aim at it, so normal cells of the lineage are hit too. HPA CD38: RNA tissue enhanced (lymphoid tissue 59 nTPM); blood lineage group enriched (B-cells 10 nTPM, dendritic cells 6 nTPM, NK-cells 18 nTPM); high antibody staining in 4 normal tissues; highest cancer staining lymphoma (1 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Multiple myeloma, Leukaemia); Open Targets associates it with 1 specific cancer type at or above 0.5 (plasma cell myeloma). (Rule 5 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas CD38 tissue","url":"https://www.proteinatlas.org/ENSG00000004468-CD38/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas CD38 pathology","url":"https://www.proteinatlas.org/ENSG00000004468-CD38/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000004468 associations","url":"https://platform.opentargets.org/target/ENSG00000004468/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:1667","ensembl":"ENSG00000004468","uniprot":"P28907","entrez":"952","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Jackson D.G. et al, J. Immunol, 1990, \"Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2319135/","biology":"CD38 is an ectoenzyme (NADase); immunomodulatory effects arise via depletion of CD38+ regulatory cells.","whereFound":["Multiple myeloma","AML (subset)"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"multiple-myeloma","pct":">95","measure":"Plasma-cell surface expression","source":"https://en.wikipedia.org/wiki/CD38"},{"cancerId":"aml","pct":"60-80","measure":"Blast expression, variable intensity","source":"https://en.wikipedia.org/wiki/CD38"}]},"route":"/targets/cd38/","neighbours":{"biomarker":[{"id":"cd38-expression","kind":"biomarker","name":"CD38 expression","route":"/biomarkers/cd38-expression/"}],"cancer":[{"id":"all-paediatric-high-risk","kind":"cancer","name":"High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)","route":"/cancers/all-paediatric-high-risk/"},{"id":"hiv-associated-lymphoma","kind":"cancer","name":"HIV-associated (AIDS-related) lymphomas","route":"/cancers/hiv-associated-lymphoma/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-transplant-eligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-eligible","route":"/cancers/myeloma-transplant-eligible/"},{"id":"myeloma-transplant-ineligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-ineligible","route":"/cancers/myeloma-transplant-ineligible/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"plasma-cell-leukaemia","kind":"cancer","name":"Plasma cell leukaemia","route":"/cancers/plasma-cell-leukaemia/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"},{"id":"smouldering-myeloma","kind":"cancer","name":"Smouldering multiple myeloma","route":"/cancers/smouldering-myeloma/"}],"drug":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"},{"id":"isatuximab","kind":"drug","name":"Isatuximab","route":"/drugs/isatuximab/"},{"id":"isb-2001","kind":"drug","name":"ISB 2001","route":"/drugs/isb-2001/"},{"id":"sg301","kind":"drug","name":"SG301","route":"/drugs/sg301/"},{"id":"sti-6129","kind":"drug","name":"STI-6129","route":"/drugs/sti-6129/"}],"term":[{"id":"b-cell","kind":"term","name":"B cell","route":"/terms/b-cell/"},{"id":"lymphoma-bio-lineage-antigen-cost","kind":"term","name":"What it costs to aim at a lineage antigen","route":"/terms/lymphoma-bio-lineage-antigen-cost/"}],"person":[{"id":"ajai-chari","kind":"person","name":"Ajai Chari","route":"/people/ajai-chari/"},{"id":"ola-landgren","kind":"person","name":"C. Ola Landgren","route":"/people/ola-landgren/"},{"id":"maria-victoria-mateos","kind":"person","name":"María-Victoria Mateos","route":"/people/maria-victoria-mateos/"},{"id":"meletios-dimopoulos","kind":"person","name":"Meletios A. Dimopoulos","route":"/people/meletios-dimopoulos/"},{"id":"philippe-moreau","kind":"person","name":"Philippe Moreau","route":"/people/philippe-moreau/"},{"id":"pieter-sonneveld","kind":"person","name":"Pieter Sonneveld","route":"/people/pieter-sonneveld/"},{"id":"sagar-lonial","kind":"person","name":"Sagar Lonial","route":"/people/sagar-lonial/"},{"id":"thierry-facon","kind":"person","name":"Thierry Facon","route":"/people/thierry-facon/"}],"collection":[{"id":"mmrf","kind":"collection","name":"Multiple Myeloma Research Foundation (MMRF)","route":"/collections/mmrf/"}],"paper":[{"id":"paper-cepheus-dara-vrd-natmed-2025","kind":"paper","name":"CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint","route":"/key-papers/paper-cepheus-dara-vrd-natmed-2025/"},{"id":"paper-maia-daratumumab-rd-nejm-2019","kind":"paper","name":"MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant","route":"/key-papers/paper-maia-daratumumab-rd-nejm-2019/"},{"id":"paper-perseus-dara-vrd-transplant-nejm-2024","kind":"paper","name":"PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma","route":"/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/"}],"institution":[{"id":"emory-winship","kind":"institution","name":"Winship Cancer Institute of Emory University","route":"/institutions/emory-winship/"}],"pathway":[{"id":"complement-in-cancer","kind":"pathway","name":"Complement in cancer","route":"/pathways/complement-in-cancer/"},{"id":"nk-cell-recognition","kind":"pathway","name":"NK-cell recognition: missing self & stress ligands","route":"/pathways/nk-cell-recognition/"}],"company":[{"id":"glenmark","kind":"company","name":"Glenmark Pharmaceuticals (Ichnos Glenmark Innovation)","route":"/companies/glenmark/"}]}}