Rare Diseases Symptoms Automatic Extraction

The novel immunotoxin HM1.24-ETA' induces apoptosis in multiple myeloma cells.

[severe combined immunodeficiency]

Despite new treatment modalities, the clinical outcome in a substantial number of patients with multiple myeloma (MM) has yet to be improved. Antibody-based targeted therapies for myeloma patients could make use of the HM1.24 antigen (CD317), a surface molecule overexpressed on malignant plasma cells and efficiently internalized. Here, a novel immunotoxin, HM1.24-ETA', is described. HM1.24-ETA' was generated by genetic fusion of a CD317-specific single-chain Fv (scFv) antibody and a truncated variant of Pseudomonas aeruginosa exotoxin A (ETA'). HM1.24-ETA' inhibited growth of interleukin 6 (IL-6)-dependent and -independent myeloma cell lines. Half-maximal growth inhibition was observed at concentrations as low as 0.3 nM. Target cell killing occurred via induction of apoptosis and was unaffected in co-culture experiments with bone marrow stromal cells. HM1.24-ETA' efficiently triggered apoptosis of freshly isolated/cryopreserved cells of patients with plasma cell leukemia and MM and was active in a preclinical severe combined immunodeficiency (SCID) mouse xenograft model. Importantly, HM1.24-ETA' was not cytotoxic against CD317-positive cells from healthy tissue (monocytes, human umbilical vein endothelial cells). These results indicate that CD317 may represent a promising target structure for specific and efficient immunotoxin therapy for patients with plasma cell tumors.

Diseases presenting "positive cells" symptom

  • canavan disease
  • carcinoma of the gallbladder
  • coats disease
  • congenital diaphragmatic hernia
  • dedifferentiated liposarcoma
  • epidermolysis bullosa simplex
  • erythropoietic protoporphyria
  • esophageal adenocarcinoma
  • hodgkin lymphoma, classical
  • severe combined immunodeficiency
  • werner syndrome
  • x-linked adrenoleukodystrophy

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