Global First-in-Class IL-6-Knockdown CD19 CAR-T Therapy ssCART-19 Shows Promising Phase I Results with Reduced Neurotoxicity and Severe CRS Risk

Cytokine Release Syndrome (CRS）AndImmune Effector Cell-Associated Neurotoxicity Syndrome (ICANS）YesLife-threatening adverse events in CAR-T clinical treatment, IL-6 is a key cytokine potentially associated with CRS and ICANS. ssCART-19 is the world's first IL-6.SilenceTheCART products, by integrating shRNA targeting IL-6, reduce the release of IL-6, thereby decreasing the incidence of severe CRS and ICANS.

Recently, the team of Professor Depei Wu and SHANGHAI UNICAR-THERAPY BIOMED-PHAMACEUTICAL TECHNOLOGY CO., LTD jointlyCompletedIL-6 GeneSilent EmpowermentOfCD19 CAR-T（ssCART-19)The research data was released inInternational authoritative hematology journal 《Blood Cancer Journal》，The title of the paper is“IL-6 knockdown anti-CD19 CAR-T cells (ssCART-19) for patients with relapsed or refractory acute lymphoblastic leukemia: phase 1 trial”。The study was approved by the Center for Drug Evaluation of the National Medical Products Administration.Phase I Study, First Author: Professor Xue Shengli,Co-Corresponding AuthorForProfessor Depei Wu, Professor Xiaowen TangAndFounder of UNICAR-THERAPY/Chief Scientist YuLeiDr. TheResearchReportedThe world's first to increase on a targeted basisIL-6 Silencing Empowerment Element in CD19 CAR-TProductTreatmentRefractory/Recurrent AcuteBLymphocytic Leukemia (Including Central Nervous System Leukemia)ThePhase I Research Results, ItsSafety and EfficacyExcellent, is expected to bring benefits to more patientsNewTreatment OptionsAnd Survival Hope。

The study was led by the Department of Hematology, First Affiliated Hospital of Soochow University, and is a single-arm, dose-escalation trial.IPhase ClinicalResearch`, aimed to evaluate`ssCART-19 in Adult Refractory/Recurrent AcuteBLymphocytic Leukemia（r/r B-ALL）Safety, tolerability, and preliminary efficacy in patients.Seventeen adult patients with r/r B-ALL received ssCART-19 infusion.Enrolled PatientsMedian AgeAt 39 years old, 47% (8/17) were associated with high-risk factors such as TP53 mutations or BCR-ABL1 fusion. The lymphodepletion regimen wasFludarabine (30 mg/m²/day) and cyclophosphamide (300 mg/m²/day) were administered from day -5 to day -3.Cells are administered in fractions (10%-30%-60%), set low（1×10⁶ CAR-positiveCell/kg）, China（5×10⁶ CAR-positiveCell/kg）, High（1×10⁷ CAR-positiveCell/kg）Three dose groups.

ResearchThe results showed,ssCART-19 treatment was generally well-tolerated, with no dose-limiting toxicity (DLT) observed. The incidence of cytokine release syndrome (CRS) was 76.5% (13/17).There is3 cases occurred Grade 3 CRS occurred, with no Grade 4 CRS; the incidence of Grade 3 CRS in the low-dose group was only 10%, significantly lower than traditional CD19 CAR-T products.17 patientsNo immune effector cell-associated neurotoxicity syndrome (ICANS) was observed.ICANS), even ifYesBaseline Merged Central Nervous System Leukemia (CNSL) in 1 patientAlsoNo neurotoxicity observed.

Efficacy evaluation at 28 days showed that 14/17 patients achieved objective response (ORR 82.4%）。Efficacy evaluation at 3 months showed that 11 of 17 patients achieved objective response (ORR 64.7%), including 8 with complete response (CR) and 3 with complete response but incomplete hematologic recovery (CRi), all of whom achieved minimal residual disease (MRD)-negative status. The ORR in the low-dose group (n=10) was as high as 80%. At a median follow-up of 20.1 months, the median duration of response (DOR) for the 14 patients achieving CR/CRi was 25.8 months (95% CI 4.8-46.9). The median progression-free survival (PFS) for all patients was 22.2 months, and the overall survival (OS) has not yet been reached.

The positive results of ssCART-19 in Phase I clinical trials make it a promising new treatment option for high-risk patients with central nervous system involvement and high tumor burden. Currently, a multi-center Phase II clinical study (NCT06367114) is underway to further evaluate the recommended Phase I dose (1x10⁶ CAR-positive).Cell/kg) in a larger cohort and continue long-term follow-up.

Research Corresponding Author: First Affiliated Hospital of Soochow UniversityWu DepeiThe professor stated："ssCART-19 Demonstrates in r/r B-ALL Patients"ExcellentEfficacy，And canSignificantImproveSafety.The objective response rate of the low-dose group reached80%, andIncidence of Grade 3 CRSOnly for10%, no ICANS events were observed.。In the medium-dose group, thereOne patient with leukoencephalopathy during the screening period did not develop ICANS after infusion and achieved remission.。This productForr/r B-ALL patients，Especially patients with leukoencephalopathy,Provided a safer treatment option. In the future, we look forward to through multi-centerPhase ⅡClinicalThe experiment further verifies itsEfficacy and Safety，to promote the early benefit of this therapy for more patients。”

Founder of UNICAR-THERAPY/Chief Scientist Dr. Yu Lei emphasized："We are very pleased to see the Phase I research results of ssCART-19 published in Blood Cancer Journal. This achievement highlights the innovation of UNICAR-THERAPY."SexSMART Gene Regulation EmpowermentPlatform TechnologySuccessful Application——ThroughshRNA-mediated IL-6SilenceDesign, Regulating from the SourceCRS-related factor release，Significantly Improve Safety and Maintain Excellent Efficacy. Thank the research team and patients for their trust. We will accelerate the promotion of global multi-center clinical layout to bring China's originalCAR-T Technology Benefits MoreMore patients。”

AboutssCART-19 Cell Injection

With Silent InterleukinThe targeted CD19 gene-engineered autologous T-cell injection (ssCART-19) with six expression functions is a globally first-in-class fourth-generation CAR-T product developed based on the unique SMART gene regulation empowerment technology platform of SHANGHAI UNICAR-THERAPY BIOMED-PHAMACEUTICAL TECHNOLOGY CO., LTD.。The ProductCan be expressed simultaneouslyCAR Structure and IL-6GeneSilent element,CanSignificantly ReduceThe release level of IL-6 factor, therebyEffectively InhibitMonocytesExcessiveActivation andDownstreamRelease of pro-inflammatory cytokines,TherebyTo mitigate severe cytokine release syndrome from a preventive perspective (CRS）AndImmune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) incidence,Significantly ImproveThe Safety of CAR-T Medication.

ssCART-19 Cell Injection is the world's first breakthroughTraditionalContraindications for CAR-T、Can be used for treatmentCentral Nervous System Leukemia (commonly known as"Brain White") Safe CAR-T Product,AlreadyObtained in the United StatesFDA Orphan Drug Designation,ByIncluded in the List of Breakthrough Therapies in China。Currently, this productCompletedPhase IExploratory Clinical Study,And has enteredKey ClinicalResearchPhase。In addition, its treatment recurrence/The latest research achievements on refractory central nervous system lymphoma have also been selected.The 67th Annual Meeting of the American Society of Hematology in 2025（ASH) Oral Report.

About the Hematology Department of the First Affiliated Hospital of Soochow University

The Hematology Department of the First Affiliated Hospital of Soochow University was established in the 1950s.The first hematology research laboratory in China was established in 1963, followed by the first thrombosis and hemostasis research laboratory in 1981. The Jiangsu Institute of Hematology was founded in 1988, and in 2002, it was approved as a national key discipline. In 2007, the Key Laboratory of Thrombosis and Hemostasis of the Ministry of Health was established, and in 2009, the Tang Zhongying Hematology Research Center was set up. It became a national key clinical specialty in 2011. The Suzhou University Hematopoietic Stem Cell Transplantation Research Institute was established in 2014, and in 2019, it was officially approved as the National Clinical Medical Research Center for Hematological Diseases. This marked the first time a national clinical medical research center in the field of hematology was established in China, representing the top national standards and strong capabilities in the field of hematology. Upholding three major research directions—bleeding and thrombotic disorders, malignant hematological tumors, and hematopoietic stem cell transplantation and cellular therapy—it has now become a leading hematology research center in China and is internationally renowned. Academic leaders, Academician Changgeng Ruan and Professor Depei Wu, have successively served as chairpersons of the Hematology Society of the Chinese Medical Association, driving the vigorous development of hematology in China.

About UNICAR-THERAPY

SHANGHAI UNICAR-THERAPY BIOMED-PHAMACEUTICAL TECHNOLOGY CO., LTD is aClinical Value-Oriented，A leading biopharmaceutical company dedicated to the innovation and translation of cutting-edge cell therapy technologies。CompanyWith multiple original core technology platforms, includingSMART Small Nucleotide Gene Regulation Empowerment Technology Platform, MADDS Antibody Innovation Drugability Technology Platform,And6HHigh StandardsProduction Quality Control Platform, etc., to systematically enhance the safety, efficacy, and accessibility of cell-based therapeutics.Currently, the company has established a billion-level gene and cell therapy research and industry center in the North Shanghai Biomedical Park. It is also committed to building an internationally leading immunotherapy tumor innovation technology transformation center, as well as an advanced and high-end genetically engineered immune cell industry chain center. As of now,CompanyHas cooperated with many well-known medical institutions at home and abroad,CumulativeSuccessfully treated thousands of patients with advanced cancer.CompanyRich product pipeline,CoverAutologousCAR-T, UniversalTypeCAR-TAndIn vivoCAR Technology: Indications Cover Hematologic Tumors and Solid TumorsAndAutoimmune diseases. Currently, there are threeFirst-in-class/First-in-safe ProductsEnterRegistered Clinical Research Phase，Several novel therapies with new targets and multiple targets are in the clinical exploration stage.