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CD38 is a myeloma surface enzyme and the target of daratumumab, which is now given as a quick under-the-skin injection.
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.
In plain words · CD38 is a myeloma surface enzyme and the target of daratumumab, which is now given as a quick under-the-skin injection.
Backbone ribbon from PDB 7DHA. RCSB PDB 7DHA. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
CD38 is a myeloma surface enzyme and the target of daratumumab, which is now given as a quick under-the-skin injection.
CD38 is an ectoenzyme (NADase); immunomodulatory effects arise via depletion of CD38+ regulatory cells.
5 products aim at CD38: antibodies, antibody-drug conjugates and bispecific antibodies. 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 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.)
Sources: Human Protein Atlas CD38 tissue; Human Protein Atlas CD38 pathology; Open Targets ENSG00000004468 associations
First described 1990. 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". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
CD38 is an ectoenzyme (NADase); immunomodulatory effects arise via depletion of CD38+ regulatory cells.
RNA: tissue enhanced (lymphoid tissue 59 nTPM), detected in many normal tissues. Blood: group enriched (B-cells 10 nTPM, dendritic cells 6 nTPM, NK-cells 18 nTPM).
Medium: Appendix, Bone marrow, Spleen.
Medium only: prostate cancer.
HPA CD38 tissue · HPA CD38 pathology · HPA protein class: CD markers
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 |
|---|---|---|---|---|
| Multiple myeloma | >95% | Plasma-cell surface expression | Wikipedia | |
| Acute myeloid leukaemia | 60-80% | Blast expression, variable intensity | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
The CD38 antibody that turned triplets into quadruplets: adding it to standard induction roughly halves the risk of myeloma progressing.
Isatuximab is Sanofi's CD38 antibody, approved in frontline transplant-ineligible myeloma (IMROZ) and, from July 2026, as an under-the-skin injection.
An Indian-discovered antibody that grips two targets on myeloma cells at once while pulling in T cells to kill them, licensed to AbbVie in 2025 in the biggest deal yet for an Indian cancer drug.
SG301 is an experimental investigational agent whose form is not stated in the registry from Hangzhou Sumgen Biotech in phase 3 trials for multiple myeloma, aimed at CD38.
STI-6129 is an experimental antibody-drug conjugate from Zhejiang ACEA Pharmaceutical in phase 2 trials for multiple myeloma, aimed at CD38.
CEPHEUS extends the quadruplet standard to patients who are not going to transplant, closing the gap between transplant-eligible and ineligible populations. It is also one of the first phase 3 trials to be designed around MRD-negativity as the primary endpoint, which could shorten future myeloma trials by years. Frailer patients still need dose-adapted approaches.
PERSEUS, with the earlier GRIFFIN and CASSIOPEIA trials, made a four-drug daratumumab quadruplet the standard for fit patients heading to transplant. It also introduced MRD-directed stopping of the antibody, a step towards treatment that is deep but not indefinite. Whether transplant itself remains necessary on top of a quadruplet is now the open question.
MAIA made a daratumumab-based triplet the standard first treatment for older or frail myeloma patients, replacing Rd alone. It proved an anti-CD38 antibody could improve survival, not just delay progression, when used up front. Quadruplets built on this backbone are now being tested in the same population.
Query for this target: (TITLE:"CD38" OR ABSTRACT:"CD38") 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 CD38, not a curated reading list.
Shares B cell, Complement in cancer, What it costs to aim at a lineage antigen, NK-cell recognition: missing self & stress ligands and the tag antibody-target.
Shares Multiple Myeloma Research Foundation (MMRF), MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint, PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma.
Shares MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, Isatuximab, PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma, Newly diagnosed multiple myeloma, transplant-eligible.
Shares Thierry Facon, Isatuximab, CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint, Newly diagnosed multiple myeloma, transplant-ineligible.
Shares Thierry Facon, MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, Newly diagnosed multiple myeloma, transplant-ineligible, Daratumumab.
Shares Multiple Myeloma Research Foundation (MMRF), Smouldering multiple myeloma, Plasma cell leukaemia, Newly diagnosed multiple myeloma, transplant-eligible.
Shares Multiple Myeloma Research Foundation (MMRF), Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-ineligible, Newly diagnosed multiple myeloma, transplant-eligible.
Shares Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-ineligible, Plasma cell leukaemia, Newly diagnosed multiple myeloma, transplant-eligible.