Next-Generation CAR T-cell Therapy: Anbal-cel with PD-1 and TIGIT Silencing for Lymphoma

Silencing the "Brakes" on CAR T Cells: What Did Anbal-cel Achieve in Relapsed Lymphoma?

A new CAR T-cell therapy developed in Korea, anbalcabtagene autoleucel (anbal-cel), showed high response rates in a phase 1/2 trial in relapsed or refractory large B-cell lymphoma (LBCL). What sets the therapy apart is that it silences two "brake" molecules in CAR T cells, PD-1 and TIGIT, at the same time. The results were published in the journal Blood by a team led by Won Seog Kim of Samsung Medical Center. Approved in South Korea in April 2026, the therapy became the country's first homegrown CAR T therapy (how cancer drugs are approved). We have previously covered lymphoma, the story of CAR T therapy and CAR T and bispecific antibodies.

Why does this matter?

Large B-cell lymphoma is the most common aggressive lymphoma in adults and the most common subtype of non-Hodgkin lymphoma (how it differs from Hodgkin lymphoma). Although most patients are cured with first-line treatment, about one in three relapses or does not respond to treatment. CAR T-cell therapy has changed treatment for these patients: the patient's own T cells are modified in the laboratory to recognize the CD19 protein on lymphoma cells and are then given back. With approved products, complete response rates range from 40% to 58%, and in a substantial share of these patients the response lasts for years (immunotherapies).

However, in more than half of patients the disease eventually progresses again. One reason is that CAR T cells exposed to the tumor for a long time become "worn out" (exhausted). PD-1 and TIGIT are "brake" molecules on the surface of T cells that the tumor uses to suppress them. In immunotherapy, drugs that block PD-1 (pembrolizumab, nivolumab) release these brakes from the outside. Anbal-cel, by contrast, silences the brakes genetically, inside the CAR T cell.

What is anbal-cel?

Anbal-cel (anbalcabtagene autoleucel) is an autologous, CD19-targeted CAR T-cell therapy developed in South Korea. A receptor that recognizes CD19 is added to the patient's T cells, while the PD-1 and TIGIT "brake" molecules that drive T-cell exhaustion are genetically silenced. It is given as a one-time infusion in relapsed or refractory large B-cell lymphoma and was approved in South Korea in April 2026.

What did the trial show?

In the phase 1 part of the multicenter, single-arm phase 1/2 trial (CRC01), three dose levels were tested in 11 patients, and no dose-limiting side effects were seen. In phase 2, 79 patients (median age 65) received the recommended dose of 2 × 10⁶ cells/kg; 73 were included in the efficacy analysis. The patients had large B-cell lymphoma (diffuse large B-cell lymphoma not otherwise specified, grade 3B follicular lymphoma, high-grade B-cell lymphoma or primary mediastinal lymphoma) without an adequate response after at least two lines of chemotherapy or after autologous stem cell transplant. While their CAR T cells were being manufactured, 64.6% of patients received bridging therapy.

Responses were linked to how much the CAR T cells expanded in the body: in responders, peak CAR T-cell levels were about 2.4 times those of non-responders (median 20,403 versus 8,580 copies/µg). The lower PD-1 and TIGIT levels in the CAR T cells of patients who stayed in complete response for at least 6 months support the biological rationale of the silencing approach; however, this association does not prove that it is what causes the durable response.

How does it compare with approved CAR T therapies?

Anbal-cel has not been compared directly with approved CAR T products. When the results of the registration trials are placed side by side, its complete response rate looks high and its rate of severe cytokine release syndrome moderate:

Values for approved products are based on the ZUMA-1, JULIET and TRANSCEND registration trials. Patient populations, use of bridging therapy, response assessment and side effect grading methods differ; the comparison is indirect.

The high complete response rate is encouraging, but what really matters in CAR T therapy is how long the response lasts. With anbal-cel, median progression-free survival is 6 months and about one in three patients is progression-free at 18 months, a rate similar to the long-term data for approved products. In other words, whether the high complete response rate translates into longer disease-free living will only become clear with longer follow-up (reading research correctly).

Side effects

• Low blood counts: 97.5% of patients had a grade 3 or higher side effect; the most common were low neutrophil counts (93.7%), low platelet counts (41.8%) and anemia (30.4%). These are largely due to lymphodepleting chemotherapy and are an expected picture with CAR T therapies.
• Cytokine release syndrome: Seen in 57% of patients; grade 3 in 8.9%, with no grade 4 cases. This condition, which presents with fever, low blood pressure and a need for oxygen, results from overstimulation of the immune system.
• Neurological side effects: Seen in 13.9% of patients; the rate of serious neurological side effects was 3.8%. This rate is lower than with some approved products, and the investigators note that it could help the therapy be given at a wider range of centers.
• Infections: Grade 3 or higher infections occurred in 25.3% of patients, and three patients had infections resulting in loss of life. Because the immune system stays weak for months after CAR T, infection prevention and monitoring are very important (immunotherapy side effects).
• A theoretical question: PD-1 and TIGIT are brakes that normally also keep T cells from overreacting. Whether silencing them will lead to new immune-related side effects in the long run needs to be assessed with long-term follow-up.

Limitations

• Single-arm trial; no comparison group.
• Short follow-up (median 8.5 months); the 18-month values are based on a small number of patients.
• The trial was conducted only in South Korea; the results need to be confirmed in other populations and health care systems.
• The rate of serious neurological side effects is reported differently across sources; the details should become clear in the full text of the paper.
• Today, in relapsed large B-cell lymphoma, bispecific antibodies (such as glofitamab and epcoritamab) and antibody-drug conjugates are also options in addition to CAR T; anbal-cel has not been compared with these either (bispecific antibodies).

The "brake silencing" approach is being studied not only in lymphoma but also in solid tumors, where CAR T is not yet effective enough; we have covered CAR T trials in brain tumors such as glioblastoma in separate articles (dual-target CAR T, B7-H3-targeted CAR T). Unlike gene-editing methods that cut a gene permanently (CRISPR), genetic silencing (knockdown) aims to reduce the gene's expression.

Tips for patients and their families

• Early evaluation: When lymphoma relapses or does not respond to initial treatment, it is important to go early to an experienced center so that CAR T or bispecific antibody options can be evaluated; manufacturing CAR T cells takes several weeks.
• Watch for symptoms: New swellings in the neck, armpit or groin, fever, night sweats and weight loss may be signs of relapse (why lymph nodes swell, lymph nodes in the armpit).
• After treatment: In the first weeks after CAR T, you need to stay close to the treatment center, report fever and any changes in alertness right away, and be careful about infections for months; the timing of vaccinations should be planned with your doctor (vaccines for people with cancer).
• When making decisions, do not hesitate to get a second opinion.

Frequently asked questions

What is anbal-cel?

Anbal-cel (anbalcabtagene autoleucel) is a CD19-targeted CAR T-cell therapy developed in South Korea. What sets it apart from others is that it genetically silences PD-1 and TIGIT, the molecules that cause T cells to become exhausted. It was approved in South Korea in April 2026 for relapsed or refractory large B-cell lymphoma.

How effective is anbal-cel?

In the phase 1/2 trial, the overall response rate in 73 patients was 75.3% and the complete response rate 67.1%. At 18 months, 35.2% of patients were progression-free and 57.3% were alive. Among those who stayed in complete response for at least 6 months, the rate of living without progression at 18 months was 79.4%. The trial was single-arm and follow-up was short.

What are its side effects?

Almost all patients had a severe drop in blood counts. Cytokine release syndrome developed in 57% (severe in 8.9%) and neurological side effects in 13.9%. Serious infection occurred in 25.3% of patients, and three patients had infections resulting in loss of life.

Is anbal-cel available in Turkey?

No. As of October 2026, it is approved only in South Korea. In Turkey, access to CAR T and bispecific antibody options for relapsed large B-cell lymphoma varies by center and reimbursement conditions; this should be discussed with your doctor.

Glossary

CAR T-cell therapy

A treatment in which the patient's T cells are modified in the laboratory to recognize cancer cells and are then given back.

CD19

A protein on the surface of lymphoma cells of B-lymphocyte origin that CAR T cells target.

PD-1 and TIGIT

Molecules on the surface of T cells that put the brakes on the immune response.

Knockdown (gene silencing)

Reducing the expression of a gene so that less of the corresponding protein is made.

T-cell exhaustion

Loss of function in T cells that have been stimulated for a long time.

Cytokine release syndrome

Symptoms such as fever and low blood pressure caused by substances released when CAR T cells are activated.

Bridging therapy

Treatment given to keep the disease under control while CAR T cells are being manufactured.

Lymphodepleting chemotherapy

Short-course chemotherapy given before the infusion so that CAR T cells can expand.