A Phase 1b Dose Expansion Study Evaluating Safety, Preliminary Anti-Tumor Activity, and Accelerated T Cell Reconstitution with NT-I7 (Efineptakin Alfa), a Long-Acting Human IL-7, Administered Following Tisagenlecleucel in Subjects with Relapsed/Refractory Large B-Cell Lymphoma

Ghobadi, Armin; Budde, Lihua E.; Galal, Ahmed; Stermer, Kristina; Bierly, Allison; Ferrando-Martinez, Sara; Lee, Byung Ha; DiPersio, John F.

doi:10.1182/blood-2022-159504

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Encouraged by our recent findings that rhIL-7-hyFc enhances CAR-T cell expansion, persistence and anti-tumor activity, a Phase 1b clinical trial is currently ongoing using rhIL-7-hyFc (efineptakin alfa, NeoImmuneTech, Inc.) following the standard of care CD19 CAR T-cell therapy in patients with Relapsed/Refractory Large B-cell Lymphoma (ClinicalTrials.gov ID: NCT05075603). Our preliminary data suggests that rhIL-7-hyFc treatment following tisagenlecleucel was safe and well-tolerated and did not induce CRS or ICANS [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

An “off-the-shelf” CD2 universal CAR-T therapy for T-cell malignancies

Xiang,

Devenport,

Carter

et al. 2023

Leukemia

Self Cite

View full text Add to dashboard Cite

T-cell malignancies are associated with frequent relapse and high morbidity, which is partly due to the lack of effective or targeted treatment options. To broaden the use of CAR-T cells in pan T-cell malignancies, we developed an allogeneic “universal” CD2-targeting CAR-T cell (UCART2), in which the CD2 antigen is deleted to prevent fratricide, and the T-cell receptor is removed to prevent GvHD. UCART2 demonstrated efficacy against T-ALL and CTCL and prolonged the survival of tumor-engrafted NSG mice in vivo. To evaluate the impact of CD2 on CAR-T function, we generated CD19 CAR-T cells (UCART19) with or without CD2 deletion, single-cell secretome analysis revealed that CD2 deletion in UCART19 reduced frequencies of the effector cytokines (Granzyme-B and IFN-γ). We also observed that UCART19ΔCD2 had reduced anti-tumor efficacy compared to UCART19 in a CD19+NALM6 xenograft model. Of note is that the reduced efficacy resulting from CD2 deletion was reversed when combined with rhIL-7-hyFc, a long-acting recombinant human interleukin-7. Treatment with rhIL-7-hyFc prolonged UCART2 persistence and increased survival in both the tumor re-challenge model and primary patient T-ALL model in vivo. Together, these data suggest that allogeneic fratricide-resistant UCART2, in combination with rhIL-7-hyFc, could be a suitable approach for treating T-cell malignancies.

show abstract

Section: Discussionmentioning

confidence: 99%