Trial will test AlloNK for SLE patients with lupus nephritis

Experimental natural killer cell therapy to be taken in combination with rituximab

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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AlloNK, an off-the-shelf experimental natural killer (NK) cell therapy being developed by Artiva Biotherapeutics, soon will enter clinical testing, in combination with rituximab, for systemic lupus erythematosus (SLE) patients with active lupus nephritis.

This follows the approval of the company’s investigational new drug application by the U.S. Food and Drug Administration (FDA). According to the company, AlloNK is the first off-the-shelf cell therapy to be cleared by regulatory authorities to enter clinical testing for an autoimmune disorder.

In SLE, the most common form of lupus, B-cells produce harmful self-reactive antibodies (autoantibodies) that target and attack the body’s own tissues. Disease symptoms are due to inflammation in various tissues and organs. Lupus nephritis is a common SLE complication that’s characterized by kidney damage and inflammation.

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Common therapeutic approaches for lupus include the use of immunosuppressants, as well as antibodies that specifically target certain immune proteins.

Rituximab, sold under the brand names Rituxan and Truxima, among others, is an antibody that targets the CD20 protein found on the surface of B-cells, leading to their destruction. While it has been used to treat some types of cancer involving B-cells and certain autoimmune diseases, its effectiveness in treating SLE and lupus nephritis is limited.

“Although rituximab has been used off-label in the treatment of SLE, rituximab alone has been shown to give incomplete B-cell depletion,” Kenneth Kalunian, MD, a clinician and professor of medicine at the University of California San Diego and a member of Artiva’s advisory board of experts, said in a press release.

AlloNK, also known as AB-101, was designed to be administered in combination with monoclonal antibodies to boost a process called antibody-dependent cellular cytotoxicity (ADCC).

ADCC is the mechanism that allows immune cells to recognize and destroy cells harboring specific molecules that are recognized by certain antibodies. It is mediated mainly by NK cells, which are an integral part of the body’s immune system, but whose levels and function may be impaired in people with SLE.

“SLE patients may have lower levels of NK cells than healthy subjects, and these cells may be functionally impaired. An effective off-the-shelf cell therapy that can be administered and managed in the community setting could be well received by lupus patients and physicians,” Kalunian said.

NK cells are ideal for off-the-shelf therapies

Compared with other immune cells, NK cells are less likely to trigger unwanted immune reactions and don’t need to be matched to a specific patient. These properties, along with their fast and cheap production, make them the perfect cell type for off-the-shelf cell therapies.

“The addition of allogeneic [from a donor] NK cells as an ADCC-enhancing therapy could significantly enhance rituximab’s ability to drive deeper levels of B-cell depletion,” Kalunian said.

AlloNK cells are collected from healthy donor umbilical cord blood and cryopreserved. Since they do not require genetic manipulation to recognize a specific protein, they are immediately ready to be used in outpatient settings.

AlloNK in clinical trials for lymphomas

When given in combination with rituximab, AlloNK has shown promising results in a Phase 1/2 trial (NCT04673617) enrolling patients with hard-to-treat B-cell non-Hodgkin lymphoma (B-NHL). The company also is testing the combination of AlloNK with the AFM13 antibody for the treatment of patients with hard-to-treat CD30-positive lymphomas in a Phase 2 trial (NCT05883449).

“AlloNK given in combination with rituximab, an anti-CD20 antibody that targets B-cells, is already driving complete responses in late line B-NHL patients in an ongoing Phase 1 study by enhancing the activity of rituximab,” said Fred Aslan, MD, CEO of Artiva.

“Our hypothesis is that AlloNK plus rituximab also has the potential to drive deep B-cell depletion in [lupus nephritis] patients with an off-the-shelf therapy that could be administered and managed in an outpatient setting,” Aslan said.