Cell therapy linked to skin improvements in scleroderma trial
Phase 1 results show meaningful skin-score improvements in 8 of 10 patients
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A single infusion of Allogene Therapeutics‘ cell therapy ALLO-329 was followed by clinically meaningful improvements in skin scores in eight of 10 people with skin-predominant systemic sclerosis (SSc), a hard-to-treat autoimmune disease.
The findings come from an ongoing Phase 1 clinical trial called RESOLUTION (NCT07085104), which is evaluating the therapy in people with SSc and two other inflammatory disorders: lupus and myositis, an inflammatory muscle disease.
Most scleroderma patients stayed off immunosuppressants
Of the 10 participants with skin-predominant SSc, nine remained off their previous immunosuppressive treatment after receiving ALLO-329. Improvements in skin scores were also observed with and without chemotherapy-based lymphodepletion.
The data from RESOLUTION, titled “Fast-Tracking the Future of Cell Therapy: ALLO-329 RESOLUTION Phase 1 Data Update,” were presented at the 2026 American College of Rheumatology (ACR) Convergence held this month.
SSc is a chronic autoimmune disease that causes the skin and connective tissues to harden and tighten. It can also affect internal organs.
In conventional CAR T-cell therapy, immune cells called T cells are collected from a patient and modified in a laboratory to carry a chimeric antigen receptor (CAR). This receptor helps the modified cells recognize and attack cells with specific markers on their surface. Before the CAR T cells are infused back into the patient, chemotherapy called lymphodepletion is typically used to reduce existing immune cells and help the modified cells work more effectively.
However, CAR T-cell therapy can involve demanding treatment procedures and carries risks. These include cytokine release syndrome (CRS), an inflammatory response that can cause high fever, low blood pressure, and trouble breathing, and immune effector cell-associated neurotoxicity syndrome (ICANS), which can cause confusion, headache, and seizures.
“CAR T has transformed what’s possible in medicine, but toxicity and treatment complexity have kept its full potential out of reach for too many patients,” Zachary Roberts, MD, PhD, president and CEO of Allogene, said in a company press release.
Off-the-shelf cell therapy designed to reduce treatment burden
ALLO-329 is an allogeneic, or off-the-shelf, therapy, meaning it uses cells from a donor rather than the patient. This allows the therapy to be manufactured in advance, potentially making it available to more patients. ALLO-329 targets two proteins: CD19 on B cells, which are involved in producing antibodies, including those associated with the immune attacks in SSc, and CD70 on activated T cells. Targeting CD70 is designed to help prevent the patient’s immune system from rejecting the donor cells.
ALLO-329 is designed to improve the balance between treatment benefits and risks for people with autoimmune diseases, including SSc, while reducing or potentially eliminating the need for conventional lymphodepletion.
Last year, the U.S. Food and Drug Administration (FDA) granted fast track designation to ALLO-329 for active, treatment-resistant diffuse SSc. This designation is intended to speed the development and review of promising treatments for serious diseases. It also allows developers to meet more frequently with the FDA.
RESOLUTION is an ongoing Phase 1 dose-escalation study of ALLO-329. The trial is testing three conditioning approaches in parallel: no lymphodepletion, lymphodepletion with cyclophosphamide, and lymphodepletion with cyclophosphamide plus fludarabine.
Allogene said the trial is designed to distinguish ALLO-329’s effects from those of chemotherapy-based conditioning. Researchers also aim to identify a treatment regimen that reduces the burden and toxicity of lymphodepletion without compromising effectiveness.
Of the 18 patients who received ALLO-329, 10 had skin-predominant SSc. Their disease duration ranged from 15 to 84 months (seven years). All had previously received immunosuppressive treatments, which were stopped before ALLO-329.
To assess skin improvements in the SSc group, researchers used the modified Rodnan Skin Score (mRSS), which measures skin thickness during a physical examination. Higher scores indicate greater skin involvement. Before ALLO-329 treatment, patients’ scores indicated severe to extensive skin involvement.
Early results show meaningful improvements in skin scores
The early data showed that, after infusion of ALLO-329, eight of the 10 SSc patients achieved and maintained a clinically meaningful decrease of at least five points in mRSS scores. Improvements were observed in most patients as early as 14 days after treatment, both with and without lymphodepletion. In four patients, mRSS scores dropped below 10 between day 28 and six months.
“The speed of improvement to me is quite remarkable, and it is life-changing from the patient’s perspective,” study investigator Vivek Nagaraja, MD, chair of the Division of Rheumatology at Mayo Clinic Arizona, who regularly treats people with SSc, said in a company webcast.
After ALLO-329, nine of the 10 SSc patients remained off standard immunosuppressive therapy.
More intensive lymphodepletion was associated with greater B-cell depletion, but patients also showed meaningful improvements without lymphodepletion. According to Allogene, these findings raise the possibility that lymphodepletion and complete peripheral B-cell depletion may not be necessary, challenging conventional thinking about CAR T-cell therapies.
Regarding safety, researchers reported no dose-limiting toxicities or cases of severe CRS, ICANS, or severe infections among all 18 patients treated with ALLO-329 as of the Sept. 21 data cutoff.
“Our ALLO-329 data … will begin to address an … important question in autoimmune disease: whether we can deliver meaningful clinical benefit with less reliance on chemotherapy-based conditioning,” Roberts said.
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