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Ursula Seidel

NEW YORK—Researchers have developed a pharmaceutical-grade, third-generation, CD19-specific antibody that reduced minimal residual disease (MRD) in pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

This chimerized, Fc-optimized antibody—4G7SDIE—was used on a compassionate-need basis in 14 patients with relapsed or refractory BCP-ALL. Nine of the patients had prior stem cell transplants.

Ursula JE Seidel, a PhD candidate at University Children’s Hospital Tubingen in Germany, discussed early results with the new antibody (poster B144) during the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Patients received 4G7SDIE infusions ranging from 5 mg/m2 to 50 mg/m2 twice a week for a year or longer.

They rarely experienced fever, nausea, or headache, according to the investigators, and all had B-cell depletion.

“The good thing about this antibody is it has a very low toxicity profile,” Seidel noted.

Upon discontinuation of therapy, B-cell counts recovered rapidly to normal levels.

The researchers followed the patients for a median of 543 days after transplant (range, 208–1137) and a median of 720 days after administration of 4G7SDIE (range, 264–1115).

Nine of the 14 patients had a reduction in MRD by 1 log or more, 2 of whom were receiving additional therapy with tyrosine kinase inhibitors.

Five patients had a reduction in MRD below the quantifiable level, and 2 patients became MRD-negative.

Six patients relapsed, and 5 of them died from relapsed disease. Two patients died of sepsis or chemotoxicity while in complete molecular remission. And 6 patients remain in complete molecular remission.

Functional characterization of 4G7SDIE

Through analysis of cells from healthy volunteers and BCP-ALL blasts of untreated and treated patients, the researchers determined that 4G7SDIE mediates enhanced antibody‑dependent cellular cytotoxicity through its improved capability to recruit FcγRIIIa-bearing effector cells.

They identified natural killer cells and γδ T cells as the main effector cells. And they determined that the FcγRIIIa-V158F polymorphism did not influence the effect of 4G7SDIE-mediated antibody‑dependent cellular cytotoxicity.

The researchers believe that the promising anti-leukemic effects of 4G7SDIE both in vitro and in vivo call for additional exploration. They are currently planning a phase 1/2 study to further assess the therapeutic activity of 4G7SDIE. end hematology article


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