Groundbreaking CAR T-Cell Therapy for Autoimmune Disease AAV Begins Recruitment in the U.S.

A revolutionary Phase 1 clinical trial is now underway, investigating SC291, an experimental CAR T-cell therapy developed by Sana Biotechnology for treating ANCA-associated vasculitis (AAV) and other autoimmune diseases. This vital study, named GLEAM (NCT06294236), is actively enrolling participants at multiple locations across the United States.

Initially launched last year, the trial began with two sites located in Aurora, Colorado, and Seattle, Washington. It has since expanded to include three additional locations in Atlanta, Baltimore, and Boston, seeking to recruit a total of up to 36 adults aged 18-75 who are suffering from AAV. Eligible candidates include individuals diagnosed with granulomatosis with polyangiitis or microscopic polyangiitis—the two most prevalent forms of AAV—who have either not responded to previous therapies or have experienced a relapse. The study also welcomes adults with specific types of lupus, a condition that shares similar kidney involvement as AAV.

Sana Biotechnology’s CEO, Dr. Steve Harr, expressed optimism about the upcoming results, stating, "We expect to share clinical data later this year from two clinical-stage programs, SC291 and SC262—our candidate for certain cancers."

Understanding Autoimmune Attacks and the Role of B-cells

Autoimmune diseases, including AAV, arise when the immune system mistakenly attacks healthy tissues, driven by self-reactive antibodies produced by B-cells. In AAV, these antibodies point neutrophils to initiate immune assaults on small blood vessels, progressively causing damage that can affect various organs, notably the kidneys and lungs.

The SC291 therapy is a CAR T-cell treatment specifically engineered to mitigate the severity of AAV and other autoimmune conditions influenced by B-cells. The innovative design targets B-cells for destruction, reducing the generation of harmful self-reactive antibodies.

The preparation of SC291 involves modifying T-cells from healthy donors in the laboratory to produce a chimeric antigen receptor (CAR) that binds to CD19, a protein found on the surface of B-cells. Once administered to patients, these modified T-cells are expected to recognize and eliminate B-cells, thereby alleviating symptoms associated with AAV.

To ensure that the patient’s immune response does not reject these donor T-cells, Sana employs a hypoimmune approach. This involves removing external proteins that could be recognized as foreign by the patient’s immune system while enhancing the production of specific proteins that signal the immune system to tolerate the donor cells.

Key Objectives and Goals of the GLEAM Study

The GLEAM study is primarily focused on assessing the safety and tolerability of a single infusion of SC291. Administration will be followed by a regimen of chemotherapy agents, including cyclophosphamide and fludarabine, designed to deplete the patient’s T-cells, thereby allowing space for the newly introduced CAR T-cells. Participants will be monitored for up to two years post-infusion.

The main endpoint of this trial is to determine the rate of adverse events and dose-limiting toxicities observed in the enrolled participants. Secondary endpoints include evaluating kidney function, the duration of remission achieved without further therapy, and the longevity of symptom relief. Additionally, clinical responses will be tracked using the Birmingham Vasculitis Activity Score (BVAS), with full remission defined by a BVAS of zero.

To ensure a thorough analysis of the therapy’s effectiveness, blood levels of SC291’s CAR T-cells will also be routinely measured across all participants.

This groundbreaking research highlights the exciting potential of CAR T-cell therapies not only for AAV but also for the broader category of autoimmune diseases, paving the way for new treatment modalities that could change the landscape of patient care. Keep an eye on this trial—its outcomes may represent a leap forward in the fight against autoimmune disorders!