CAR-T 2.0: Expanding Access, Speed, and Precision

Following the 2026 Tandem Meetings, Yan Leyfman, MD, from NewYork–Presbyterian Hospital and a hematologic malignancies board member for the journal ONCOLOGY^®, outlined key advances that emerged from the conference. He noted that this year’s data reflect a critical transition from early proof-of-concept innovation to real-world refinement in safety, access, manufacturing, and durability of cellular therapies.

Leyfman identified the following themes based on this year’s presentations:

1. Aggressive B-Cell Lymphoma: Next-Gen CAR-T
   1. A standout presentation showed late-breaking phase 1 trial (NCT06343311) data for EB-103, a CD19 TCR-mimetic CAR-T construct.¹
   2. At its recommended dose, EB-103 achieved 100% overall and complete response (CR) rates, with predominantly grade 1/2 cytokine release syndrome (CRS) and no high-grade neurotoxicity.
2. Dual-Targeting CAR-T: KITE-753
   1. Dual-target CD19/CD20 CAR T-cell therapy KITE-753 drew attention in a phase 1 study (NCT04989803).²
   2. Early data showed high complete response rates and no grade 3 or higher CRS or immune effector cell-associated neurotoxicity syndrome (ICANS), signaling a safer profile with rapid manufacturing timeline of approximately 13 days.
3. CLL-Specific Optimization
   1. In chronic lymphocytic leukemia (CLL), the LV20.19 CAR-T construct delivered deep responses in heavily pretreated patients, with high minimal residual disease (MRD) negativity and long progression-free survival in a phase 1/2 trial (NCT04186520).³
   2. However, a new inflammatory syndrome, immune effector cell–associated hemophagocytic syndrome–like syndrome (IEC-HS), emerged.
4. Off-the-Shelf Cellular Products
   1. Updated data on CB-011, an immune-cloaked allogeneic anti-BCMA CAR-T, showed an approximately 92% overall response rate with strong CR rates and no graft-versus-host disease (GVHD).⁴
   2. If safety and durability hold as cohorts expand, scalable products like this could help overcome current logistical and access barriers.
5. Beyond T Cells: Innate Immune Platforms
   1. Autologous, repolarized macrophage therapy RB-1355 demonstrated systemic activity in heavily pretreated lymphomas, with rapid manufacturing and minimal toxicity, in a phase 1 trial.⁵
6. Supportive Care Breakthroughs
   1. Phase 3 trial (NCT03073967) data for pritelivir in refractory HSV infection showed superior healing and safety vs conventional treatment.⁶

Altogether, Leyfman noted how these advances may meaningfully expand patient access, improve real-world tolerability, and solidify durability for cellular therapies across hematologic cancers.

References

1. Esteghamat N, Wang P, Zimdahl B, Liu C, Abedi M. Phase 1 study of CD19 ARTEMIS T cells (EB-103) in patients with aggressive B-cell non-Hodgkin lymphoma. Presented at: 2026 Tandem Meetings; February 4–7, 2026; Salt Lake City, UT. Presentation LBA-1.
2. Dahiya S, Ulrickson M, Yared J, et al. A phase 1 study of KITE-753 or KITE-363 in patients with relapsed/refractory B-cell lymphoma: initial safety and preliminary efficacy of KITE-753 and updated results of KITE-363. Presented at: 2026 Tandem Meetings; February 4–7, 2026; Salt Lake City, UT. Presentation 74.
3. Shah N, Murthy GSG, Atallah EL, et al. Dual targeted lentiviral transduced anti-CD20/anti-CD19 (LV20.19) CAR T cells for relapsed, refractory CLL. Presented at: 2026 Tandem Meetings; February 4–7, 2026; Salt Lake City, UT. Presentation 75.
4. Rossi A, Costa L, Clark WB, et al. CB-011, an allogeneic anti-BCMA CAR-T cell therapy with immune cloaking, for patients with relapsed/refractory multiple myeloma (r/r MM): dose escalation results from the CaMMouflage phase 1 trial. Presented at: 2026 Tandem Meetings; February 4–7, 2026; Salt Lake City, UT. Presentation LBA-2.
5. Strati P, Feldman T, Kidder K, et al. Intratumoral cellular therapy with autologous activated M1 Sirpα-low macrophages in non-hodgkin lymphoma: clinical results from a first-in-human phase 1 study. Presented at: 2026 Tandem Meetings; February 4–7, 2026; Salt Lake City, UT. Presentation 76.
6. Papanicolaou G, Avery R, Workowski K, et al. Pritelivir demonstrated superior efficacy compared to investigator’s choice treatment for refractory herpes simplex virus infections in immunocompromised patients: PRIOH-1, phase 3 safety and efficacy. Presented at: 2026 Tandem Meetings; February 4–7, 2026; Salt Lake City, UT. Presentation LBA-3.