CD38 is a powerful disease marker for human leukemias and myelomas, is directly involved in the pathogenesis and outcome of human immunodeficiency virus infection and chronic lymphocytic leukemia, and controls insulin release and the development of diabetes.
CD38-targeting antibodies have a favorable toxicity profile in patients, and early clinical data show a marked activity in MM, while studies in other hematological malignancies are ongoing.
CD38 MoAbs have emerged as a novel and ultimately very promising immunotherapeutic agent for MM because of its ability to induce MM cytotoxicity through both arms of the adaptive immune responses.
CD38 is an important therapeutic target in myeloma, therefore, regulation of myeloma metabolism may play a role in the activity of this therapeutic approach.
CD38 and SLAMF7 are the main surface molecules leading to the development of monoclonal antibodies (mAbs) recently approved for the treatment of relapsing MM patients.
A novel dual-cytokine-antibody fusion protein, consisting of an antibody directed against CD38 [a tumor-associated antigen mainly expressed on the surface of multiple myeloma (MM) cells], simultaneously fused to both tumor necrosis factor ligand superfamily member 10 (TRAIL) and interleukin-2 (IL2), was designed, expressed and purified to homogeneity.
Addition of daratumumab, an anti-CD38 to trigger antibody-dependent cell-mediated cytotoxicity, improved the anti-MM response for all subsets and degranulation of the KIR-NKG2A- "unlicensed" subset was comparable to KIR+ or NKG2A+ licensed subsets.
Anti-CD38 interference in pre-transfusion immunohaematology tests is a particular problem in patients being treated with daratumumab for multiple myeloma as many will require RBC transfusions during their disease treatment.
As of July 2017, antibodies clinically available in Japan for the treatment of multiple myeloma are elotuzumab against SLAMF7 and daratumumab against CD38.
At this moment several CD38 antibodies are at different phases of clinical testing, with daratumumab already approved for various indications both as monotherapy and in combination with standards of care in MM.
Bone marrow (BM) specimens were collected consecutively and analyzed using a routine PCM panel (CD38/CD138/CD45/CD19/CD20/CD28/CD56/CD117, cyto-kappa/lambda).
Consistently, we found that Daratumumab reacted with CD38 expressed on monocytes and its binding inhibited <i>in vitro</i> osteoclastogenesis and bone resorption activity from bone marrow total mononuclear cells of MM patients, targeting early osteoclast progenitors.
CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls.