Hyleukin-7 (efineptakin alfa)

As TGF-β impairs CD8+ T cell function and antagonizes IL-7 signaling, we developed a bifunctional fusion protein, recombinant human IL-7 (rhIL-7)-hyFc-sTBRII (IL7-TBRII), by fusing a TGF-β trap (Fc-TBRII) to rhIL-7-hyFc (IL7-Fc)...Furthermore, IL7-TBRII reduced metastasis in the 4T1 breast cancer model by reshaping the immune cell composition, and demonstrated synergistic efficacy when combined with radiotherapy or anti-CTLA-4 therapy in the EMT6 breast tumor model. These findings suggest that dual modulation of the IL-7 and TGF-β pathways by IL7-TBRII effectively reprograms the immune microenvironment in both primary and metastatic tumors, particularly by promoting CD8+ T cell activation and infiltration, thus offering a promising strategy to improve clinical responses to immunotherapy.

P1, N=24, Not yet recruiting, Washington University School of Medicine | Trial completion date: Apr 2028 --> Aug 2028 | Initiation date: Oct 2025 --> Feb 2026 | Trial primary completion date: Jul 2027 --> Nov 2027

P1/2, N=42, Active, not recruiting, Washington University School of Medicine | Trial completion date: Jan 2032 --> Apr 2028

P1, N=12, Completed, National Institute of Neurological Disorders and Stroke (NINDS) | Recruiting --> Completed | N=18 --> 12

We discovered a synergistic effect between NT-I7 and anti-PD-1 (Pembrolizumab) that notably augments immunotherapeutic efficacy through the expansion of TCM cells and sustained cytotoxicity. In sum, our humanized model reveals that NT-I7 holds great promise as a next-generation therapy to enhance clinical responses and patient care.

A dose range of 0.6-1.2 mg/kg administered at intervals of 6 to 12 weeks was suggested as feasible for the RP2D in further clinical trials. A population PK-PD modeling and simulation results demonstrated a strong exposure-response relationship for ALC across dosing intervals, underscoring the mechanism-based therapeutic potential of rhIL-7-hyFc in cancer immunotherapy.

P1, N=17, Completed, NeoImmuneTech | Recruiting --> Completed | N=57 --> 17 | Trial completion date: Feb 2026 --> Mar 2025

We found that the combination of rhIL-7-hyFc and DNA PCV treatment prolonged neoantigen-specific CD8+ T cell responses, improved functional memory as measured based on in vivo cytotoxicity, and increased the number of neoantigen-specific tumor-infiltrating lymphocytes (TILs), resulting in improved prophylactic tumor protection and durable memory responses. Our findings support the potential of rhIL-7-hyFc to enhance the efficacy of PCVs and suggest clinical utility for adjuvant rhIL-7-hyFc in cancer immunotherapy.

P1, N=40, Not yet recruiting, Washington University School of Medicine

This study demonstrates the ability of efineptakin alfa (NT-I7) to potentially augment the clinical efficacy of cancer immunotherapy by inducing tertiary lymphoid structures in the tumor microenvironment.

P1/2, N=215, Completed, NeoImmuneTech | Active, not recruiting --> Completed

Eligible HGG patients had CD4 counts <300 cells/mm3 after 5 weeks of standard chemoradiation and were receiving either ≤0.75 or ≥4 mg/day of dexamethasone. Correlative immune profiling revealed increased Ki67 expression in CD4 (P < .005) and CD8 (P < .05) after one week, along with the expansion of CD4 and CD8 T-cell subsets and CD56 + natural killer cells. NT-I7 is well tolerated and effectively increases lymphocyte and CD4 counts in severe TRL patients, regardless of glucocorticoid use, suggesting its potential to mitigate TRL and improve outcomes in HGG.