Moxetumomab

Moxetumomab refers to a monoclonal antibody fragment used as the targeting component of the recombinant immunotoxin moxetumomab pasudotox. The antibody fragment binds to CD22, a molecule expressed on the surface of many B cells, including malignant cells in certain hematologic cancers. In the constructed immunotoxin, the CD22-binding fragment is fused to a truncated Pseudomonas exotoxin A (PE38) to deliver a cytotoxic payload to the cancer cell.

Mechanism of action

When moxetumomab binds CD22, the complex is internalized by the cell. The linked toxin then inhibits protein synthesis, leading to cell death. By combining targeted binding with toxin-mediated cytotoxicity, the therapy aims to selectively kill CD22-positive malignant B cells while limiting activity against CD22-negative cells.

Clinical development and approval

Moxetumomab pasudotox was developed for CD22-expressing B-cell malignancies, most notably hairy cell leukemia (HCL). In the United States, it received regulatory approval for adults with relapsed or refractory HCL after at least two prior therapies. The product is marketed under the brand name Lumoxiti in some regions.

Administration and monitoring

The therapeutic is given by intravenous infusion on a defined schedule, typically in 28-day cycles with infusions on select days (for example, days 1, 3, and 5 of each cycle) and up to several cycles based on response and tolerability. Because of potential serious toxicities, patients require careful monitoring for signs of capillary leak syndrome, hemolytic uremic syndrome, hepatic abnormalities, and other adverse effects. Dose adjustments or discontinuation may be necessary in response to toxicity.

See also

CD22, hairy cell leukemia, recombinant immunotoxins.