A single administration of hIL-7-hyFc induces long-lasting T-cell expansion with maintained effector functions

Abstract

Interleukin-7 (IL-7) is an essential cytokine for T-cell homeostatic proliferation and maintenance. Clinical studies have shown the potential benefits of IL-7 therapy in various diseases associated with lymphopenia. However, the kinetics of the T-cell response to a single administration of IL-7 in humans have not been fully elucidated. Here, we investigated the effects of Fc-fused long-acting recombinant human IL-7 (hIL-7-hyFc, efineptakin alfa) on lymphocytes in healthy adults after a single subcutaneous or intramuscular administration. Administration of hIL-7-hyFc increased the CD8+ and CD4+ T-cell numbers up to 2.5-fold, with corresponding upregulation of Ki-67 and Bcl-2 expression, peaking at day 3 or 7. Regulatory T cells did not expand. Among CD8+ and CD4+ T cells, all T-cell subsets (TN, TEM, TCM, TEMRA, and TSCM) increased for 56 days. The TCR repertoire diversity of naïve CD8+ and CD4+ T cells was increased by hIL-7-hyFc, while the memory T-cell subsets did not differ between D56 and D0. Transcriptomic analysis revealed that hIL-7-hyFc induced robust T-cell expansion without changes in gene expression profiles associated with T-cell functions or genes related to T-cell exhaustion, senescence, and anergy. The effector functions of antigen-specific CD8+ T cells were preserved after hIL-7-hyFc administration. Our results suggest that hIL-7-hyFc administration induced a sustained increase in the numbers of CD8+ and CD4+ T cells, but not regulatory T cells, without qualitative changes. These results support the potential of hIL-7-hyFc as a treatment for patients with compromised T-cell immunity or as a vaccine adjuvant.

Higher T central and lower effector memory cells in bipolar disorder: A differentiation abnormality?

“…The rhIL-7 treatment led to increases in CD4 + T cells in both peripheral blood and tissues. Regarding the newer drug Efineptakin-α, administration in healthy adults induced a sustained increase in the numbers of naïve, T CM , T EM and T EMRA CD4 + and CD8 + T cells without qualitative changes ( Kim et al, 2022 ). The authors concluded that hIL-7-hyFc is a potential treatment for patients with compromised T-cell immunity.…”

Anti-myeloma efficacy of CAR-iNKT is enhanced with a long-acting IL-7, rhIL-7-hyFc

“… 16 A recombinant human interlukin-7 (IL-7) with an extended half-life (rhIL-7-hyFc; efineptakin α) significantly increased expansion of T cells in patients with cancer and healthy volunteers. 17 , 18 Our group demonstrated that mice with tumor engraftment treated with CAR-Ts plus rhIL-7-hyFc had dramatic expansion of CAR-Ts and significantly better tumor control than CAR-T–treated mice. 19 These studies provided rational for an ongoing clinical trial combining rhIL-7-hyFc and CD19 CAR-Ts in patients with relapsed/refractory large B-cell lymphoma (NCT05075603).…”

Engineering cytokines for cancer immunotherapy: a systematic review

“…Moreover, it was designed to minimize the loss of the bioactivity of drug candidates and prevent ADCC- or CDC-mediated cell killing effects. Notably, NT-I7 enhances T-cell-mediated antitumor immunity through multiple mechanisms, including expansion of the TCR repertoire; sensitization of T cells to weaker antigens; boosting naïve T cells, stem cell-like memory T cells (T SCM ) and memory T cells; promotion of memory T-cell differentiation; enhancement of T-cell trafficking and infiltration into tumors; augmentation of the antigen-specific T-cell response; antagonization of T-cell exhaustion and other inhibitory networks; and stimulation of the proinflammatory cytokine milieu in the TME ( 113 ).…”