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Cancer

Durable Responses and Improved Survival in Patients with Relapsed or Refractory Large B-Cell Lymphoma Demonstrated by Autologous CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy

Strategic Insights

— 1 min read

Researchers at the H. Lee Moffitt Cancer Center have reported single-cell RNA sequencing (scRNA-seq) data on 57 pre-infusion CAR T-cell products from axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) patients treated as standard-of-care for relapsed or refractory large B-cell lymphoma (R/R LBCL). The study found that axi-cel is comprised of more CD4 central memory, CD8 central memory, and CD8 effectors, while tisa-cel is comprised of more proliferative CD4 and CD8 cells. Axi-cel also had greater expression of immune response pathways and protein synthesis and trafficking pathways compared to tisa-cel.

Key Takeaways:

  • The researchers found that axi-cel and tisa-cel are markedly different products, with axi-cel having a higher proportion of CD4 central memory, CD8 central memory, and CD8 effectors, and tisa-cel having a higher proportion of proliferative CD4 and CD8 cells.
  • Axi-cel CAR+ cells had vastly different gene expression than axi-cel CAR- cells, while tisa-cel CAR+ cells were highly similar to tisa-cel CAR- cells.
  • The study suggests that axi-cel is less differentiated and has greater immune activation compared to tisa-cel, potentially accounting for its greater efficacy and toxicity in patients.
  • Tisa-cel is adversely affected by its manufacturing rather than by the CAR construct.
  • The study provides evidence that the differences in efficacy and toxicity between axi-cel and tisa-cel might be attributed to their manufacturing processes.

Statistics:

  • 39 axi-cel patients were included in the study, while 18 tisa-cel patients were included.
  • The study analyzed 57 pre-infusion CAR T-cell products from the two treatments.
  • Axi-cel CAR+ cells had higher expression of immune response pathways and protein synthesis and trafficking pathways compared to tisa-cel (p < 0.001).
  • Tisa-cel CAR+ cells were highly similar to tisa-cel CAR- cells (p < 0.01).

Sources:

  • Comparison of axicabtagene ciloleucel and tisagenlecleucel patient CAR-T cell products by single-cell RNA sequencing. Journal for ImmunoTherapy of Cancer, 2025,13(7). (Journal for ImmunoTherapy of Cancer - http://www.immunotherapyofcancer.org/)
  • The publisher for Journal for ImmunoTherapy of Cancer is BMJ Publishing Group.
  • A free version of this journal article is available at https://doi-org.sdpl.idm.oclc.org/10.1136/jitc-2025-011807.

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