Dosing begins in trial of AlloNK, NK cell therapy for lupus nephritis

Study involves patients who have relapsed, not responded to treatment

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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The first patient has been dosed in the U.S. as part of a clinical trial testing AlloNK, an experimental natural killer (NK) cell therapy candidate, in patients with lupus nephritis, one of the most common and severe complications of lupus.

The open-label Phase 1 trial (NCT06265220) is running as a collaboration between Lupus Therapeutics and Artiva Biotherapeutics, and will test the safety and efficacy of AlloNK in adults whose lupus nephritis has returned or didn’t respond to standard-of-care treatments.

Artiva said participants will receive AlloNK in combination with rituximab (sold as Rituxan, among other brands) or obinutuzumab (sold as Gazyva), two B-cell-depleting antibody-based therapies. Both target CD20, a protein found on the surface of B-cells, ultimately killing them.

Before receiving treatment, patients must undergo a process called lymphodepletion, in which chemotherapy agents are given to wipe out a patient’s disease-causing immune cells.

“Lupus nephritis is among the most severe manifestations of systemic lupus erythematosus,” Kenneth Kalunian, MD, professor of medicine and director of the University of California San Diego Lupus Center, said in an Artiva press release. “Many patients do not respond to standard therapies. Examining new treatments could provide more novel options for this patient demographic.”

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Lupus nephritis seen in as many as 2 of 3 U.S. lupus patients

In lupus, B-cells are dysfunctional and overactive, driving the production of harmful antibodies directed against a patient’s own healthy tissues. This leads to excessive inflammation and organ damage. When this attack is directed against the kidneys, it can lead to lupus nephritis.

As many as two of every three lupus patients in the U.S. are estimated to develop lupus nephritis. Current treatments include the use of immunosuppressants and antibodies that specifically target certain immune proteins, but their efficacy is limited.

AlloNK was designed to boost the effectiveness of antibody-based therapies that deplete disease-causing B-cells. It is an allogeneic therapy, composed of NK cells derived from the umbilical cord blood of healthy donors.

With its manufacturing platform, Artiva can grow enough active NK cells from healthy donors to treat hundreds or thousands of patients. The cells can be frozen and stored for ready, off-the-shelf use, offering the opportunity for repeat dosing in outpatient settings. Compared with other immune cells used in cell therapies, NK cells also have a lower risk of triggering unwanted immune reactions and don’t require genetic manipulation to recognize a specific protein on B-cells.

“We are excited to bring AlloNK to patients with autoimmune disease,” said Fred Aslan, MD, CEO of Artiva. “To our knowledge, this is the first time a patient has received an allogeneic NK cell therapy candidate in a U.S. clinical trial for treatment of an autoimmune disease.”

According to the company, AlloNK has shown promising activity in a Phase 1/2 trial (NCT04673617) in patients with hard to treat B-cell non-Hodgkin lymphoma (NHL), a type of blood cancer, when given along with rituximab.

“We are encouraged by the activity of AlloNK in our NHL trial, demonstrating AlloNK’s ability to drive B-cell depletion and helping validate the therapy’s potential mechanism of action,” Aslan said. “Furthermore, our ability to combine AlloNK with CD20, CD19, or CD38 directed monoclonal antibodies gives AlloNK the versatility to target distinct B-cell subpopulations across different autoimmune diseases.”