KLRG1 Cell Depletion Offers Novel Therapeutic Strategy for T-Cell Lymphoma

Khyati Maulik Kariya, PhD, and Kusha Chopra, BS, of Massachusetts General Hospital, joined Blood Cancers Today to discuss their research at the Salvia Jain Lab on KLRG1 cell depletion as a novel therapeutic strategy for patients with T-cell lymphoma.

“KLRG1 is expressed predominantly on late differentiated and [terminally differentiated effector memory cell] populations and [natural killer (NK)] cells,” said Dr. Kariya. “We expect its expression to be high in mature T-cell and NK-cell neoplasms, and the therapeutic antibody designed to deplete KLRG1-positive cells might carry a potential cure for this disorder.”

Dr. Kariya and colleagues found that treatment with the monoclonal antibody 208 alone, and in combination with duvelisib, extended survival in the cell lines and patient-derived xenografts.

These findings have been translated into a multicenter, open-label, phase I/II dose-escalation trial, which is actively enrolling patients with T-cell lymphoma and anemia or neutropenia.

“The KLRG1 project emphasizes the advantages of the treatment combination of duvelisib, a commonly used kinase inhibitor that prevents cancer cells from multiplying, and the anti-KLRG1 antibody that can selectively deplete highly toxic T cells while sparing important immune cells such as regulatory T cells and central memory T cells,” Chopra added. “This combination treatment truncated tumor burden substantially by leveraging the potency of repolarized macrophages.”