Health Library · Technology & Clinical Pipeline

Anbal-cel Explained: Design, Clinical Data, and Manufacturing Pathway

Educational scientific overview · Updated 2026 · For patients, families and referring physicians

Anbalcabtagene autoleucel (anbal-cel; project code CRC01; origin brand RIMQARTO®) is an autologous, next-generation CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy developed by Curocell Inc[cite: 4, 5, 7, 10, 11]. On April 29, 2026, anbal-cel received full regulatory approval from the South Korean Ministry of Food and Drug Safety (MFDS) for adult patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) or primary mediastinal large B-cell lymphoma (PMBCL) after two or more prior lines of systemic therapy[cite: 1, 4, 7, 11].

Unlike conventional second-generation CAR-T products, anbal-cel incorporates Curocell's proprietary OVIS™ (Overcome Immune Suppression) platform[cite: 4, 5, 8, 10, 11]. This platform utilizes a single "two-in-one" lentiviral vector to express an anti-CD19 CAR alongside dual short hairpin RNA (shRNA) cassettes that knock down two key immune checkpoint receptors—PD-1 and TIGIT—simultaneously upon T-cell activation[cite: 4, 5, 8, 10, 11].

Through a formal international technology-transfer partnership, Biruni Cell Therapy (BCT) has established local Good Manufacturing Practice (GMP) production capabilities at Biruni Teknopark in Istanbul, Türkiye[cite: 1, 4, 9]. This brings a clinically validated, approved-origin cell therapy into local manufacturing and TİTCK regulatory pathways[cite: 1, 4, 6, 9].

1. Molecular Design & The OVIS™ Technology Platform

The Problem of T-Cell Exhaustion

While standard CD19 CAR-T cells produce deep initial remissions, a significant proportion of patients experience relapse or resistance[cite: 4, 5, 7]. A major biological driver of failure is T-cell exhaustion[cite: 4, 5, 8]. Chronic antigen exposure within the tumor microenvironment upregulates inhibitory checkpoint receptors on the surface of CAR-T cells[cite: 4, 5, 8]. Engagement of PD-1 with its ligands (PD-L1/PD-L2) and TIGIT with its ligands (CD155/CD112) delivers potent inhibitory signals that impair CAR-T proliferation and accelerate terminal differentiation[cite: 4, 5, 8].

Preclinical Selection Rationale (Molecular Therapy, 2022)

In foundational preclinical research published in Molecular Therapy (Lee et al., 2022), scientists evaluated multiple dual-checkpoint downregulation combinations within the same anti-CD19 CAR-T framework[cite: 5, 8]:

• PD-1 + TIM-3: Failed to improve in vivo antitumor efficacy compared to single PD-1 knockdown[cite: 5, 8].
• PD-1 + LAG-3: Severely compromised CAR-T activity and mouse survival[cite: 5, 8].
• PD-1 + CTLA-4: Showed no significant additive benefit in xenograft models[cite: 5, 8].
• PD-1 + TIGIT (Selected): Demonstrated unique cooperative synergy—superior tumor clearance, enhanced expansion, and extended overall survival[cite: 5, 8].

The study revealed a functional division of labor: PD-1 downregulation primarily enhances short-term effector function and cell killing under PD-L1 pressure, whereas TIGIT downregulation primarily preserves an early central memory ($T_{CM}$) phenotype, prevents terminal differentiation ($CD57^+CD27^-$), and protects co-stimulatory signaling through the CD226 pathway[cite: 5, 8].

2. Clinical Evidence: Pivotal Phase 1/2 Study (Blood, 2026)

The definitive clinical characterization of anbal-cel in relapsed or refractory large B-cell lymphoma (r/r LBCL) was reported in Blood (Kim et al., June 2026)[cite: 5, 8, 10, 11].

Trial Population & Baseline Risk Profile

The CRC01-01 trial (NCT04836507) enrolled heavily pretreated, high-risk patients across six Korean medical centers[cite: 5, 8, 10, 11]. Among the 79 infused patients (safety set), median age was 65 years (53.2% aged $\ge65$), 71.8% had non-GCB histology, 64.0% were refractory to their last therapy, and 64.6% required bridging therapy prior to infusion[cite: 5, 8, 10].

Outcome Durability in the Long-Term Response (LR) Subgroup

Patients maintaining a Complete Response at 6 months were classified as the Long-Term Response (LR) group ($n=33$)[cite: 5, 6, 8]. Landmark survival in this subset was exceptionally high:

• 12-Month PFS in LR group: 92.6% | 18-Month PFS: 79.4%[cite: 5, 6]
• 12-Month OS in LR group: 96.4% | 18-Month OS: 83.9%[cite: 5, 6]

Translational blood analyses demonstrated that durable response strongly correlated with significantly greater peak in vivo CAR-T expansion ($C_{max}$ 20,403 vs. 8,580 copies/$\mu$g in non-responders), lower surface PD-1/TIGIT expression on Day 14, and preservation of central memory ($T_{CM}$) cellular phenotypes[cite: 5, 6, 8, 10].

Five-Year Relapse-Free Milestone

In February 2026, Curocell reported that an early Phase 1 participant with heavily pretreated r/r LBCL maintained a continuous Complete Response for five years post-infusion without recurrence or progression, assessed by treating physicians as clinically cured[cite: 11].

3. Comparative Effectiveness: Anbal-cel vs. Tisagenlecleucel (Kymriah®)

A Matching-Adjusted Indirect Comparison (MAIC) published in Cancer Research and Treatment (Seo et al., 2025/2026) evaluated individual patient data from the anbal-cel trial ($n=79$) against published aggregate data from the pivotal JULIET trial of tisagenlecleucel (tisa-cel; $n=115$)[cite: 4, 5, 8, 10].

4. Safety and Toxicity Profile

In the Phase 2 safety set ($N=79$), adverse events were consistent with expected cellular therapy mechanisms[cite: 5, 6, 8, 10, 11]:

• Cytokine Release Syndrome (CRS): Any-grade CRS occurred in 57.0% of patients; Grade 3 CRS occurred in 8.9%[cite: 5, 6, 8, 10, 11]. No Grade 4 or Grade 5 CRS events occurred[cite: 4, 5, 6, 8, 10, 11]. Median time to onset was 1 day[cite: 5, 6, 8, 10].
• Neurologic Toxicity (ICANS): Overall neurologic events occurred in 13.9% of patients, with Grade $\ge3$ ICANS reported in 3.8%[cite: 4, 5, 6, 8, 10, 11]. This represents a lower incidence of high-grade neurotoxicity than historical benchmarks reported in ZUMA-1 (28%) or TRANSCEND (10%)[cite: 5, 8].
• Hematologic Toxicity & Infections: Grade $\ge3$ neutropenia occurred in 93.7%, and serious infections occurred in 25.3% of patients[cite: 5, 6, 8, 10, 11].

5. Local GMP Manufacturing & Quality Control Pathway

Autologous CAR-T production follows a strict vein-to-vein workflow: leukapheresis collection $\rightarrow$ T-cell selection & activation $\rightarrow$ lentiviral transduction $\rightarrow$ bioreactor expansion with daily metabolic monitoring $\rightarrow$ automated harvest & cryopreservation $\rightarrow$ orthogonal release testing[cite: 4, 8, 9, 10].

At the Biruni Teknopark facility in Istanbul, product release by Biruni Cell Therapy (BCT) relies on orthogonal multi-layered testing[cite: 1, 4, 8, 9]:

1. Identity & Phenotype (FACS): $CD3^+$ T-cell gating, CAR-positive percentage, and $CD4/CD8$ ratio[cite: 8].
2. Genetic Dose (qPCR/ddPCR): Vector Copy Number (VCN) per diploid genome and residual plasmid DNA controls[cite: 8].
3. OVIS™ Function Control: Flow cytometric verification of PD-1 and TIGIT knockdown on activated CAR+ T cells[cite: 4, 8].
4. Potency (ELISA): Antigen-specific Interferon-gamma (IFN-$\gamma$) secretion following CD19 target challenge[cite: 8].
5. Safety Assays: Rapid PCR mycoplasma, endotoxin limits, sterility, and replication-competent lentivirus (RCL) screening[cite: 8].

6. Expanded Pipeline Horizons

The anbal-cel clinical program is expanding beyond systemic lymphoma into additional B-cell disorders[cite: 4, 6, 7, 10]:

• Adult Relapsed/Refractory B-ALL: Currently evaluated in Phase 1/2 cohorts under NCT04836507[cite: 4, 6, 10].
• Primary & Secondary CNS Lymphoma (NCT07062627): A dedicated Phase 2 pilot study sponsored by Asan Medical Center is evaluating anbal-cel in primary or secondary central nervous system DLBCL[cite: 6, 10].
• Severe Refractory Lupus Nephritis (NCT07364396): The Phase 1/2 CRC01-02 trial is assessing anbal-cel for deep CD19 B-cell depletion in severe refractory SLE[cite: 6, 10]. In March 2025, Seoul St. Mary's Hospital administered anbal-cel to a patient with refractory lupus nephritis under an MFDS treatment-purpose route, reporting complete cessation of immunosuppressants and early proteinuria improvement without acute toxicities at one month[cite: 7].

Key Takeaways

• Target + Function Protection: Anbal-cel combines standard CD19 recognition with dual shRNA knockdown of PD-1 and TIGIT via Curocell's OVIS™ platform[cite: 4, 5, 8, 10, 11].
• High Response Rates: Achieved an ORR of 75.3% and a Complete Response rate of 67.1% in pivotal Phase 2 trial results ($n=73$)[cite: 4, 5, 6, 8, 10, 11].
• Durable Remissions: 18-month overall survival was 83.9% among long-term complete responders, with single-patient cure reported at 5 years post-infusion[cite: 5, 6, 11].
• Manageable Safety: Grade 3 CRS occurred in 8.9% with zero Grade 4/5 CRS events; high-grade neurotoxicity was low at 3.8%[cite: 4, 5, 6, 8, 10, 11].
• Local GMP Localization: Local manufacturing in Türkiye via Biruni Cell Therapy provides domestic access to an approved-origin CAR-T therapy[cite: 1, 4, 9].