A phase 1 open-label pilot study of low-dose interleukine-2 immunotherapy in patients with Alzheimer's disease

Abstract

Trial registration: ClinicalTrials.gov Identifier: NCT05821153, Registered April 20 2023, Retrospectively registered, https://classic.

Clinicaltrials: gov/ct2/show/NCT05821153.

Fig. 1

Effect of low-dose IL-2 treatment on immune parameters and cognitive status in AD subjects. a Percentage of FOXP3⁺CD25^high CD4 T cells (i.e.,Tregs) was amplified 3 days following each IL-2 treatment cycle and returned to baseline before the next cycle. b The suppressive function of Tregs at both 1:1 and 1/2:1 Treg:Tresp ratios improved throughout the 4-month IL-2 treatment phase and reached higher levels on days 8, 38, 60, 68 and 98 of IL-2 treatment phase, compared to the baseline levels (D0). After completion of IL-2 treatment phase, the suppressive function of Tregs trended toward baseline levels on days 120 and 168. c CD25 MFI in Treg population was increased following IL-2 administration on days 8, 38 and 68. d Transcript expressions of IL-1β, TNF and IL-6 in monocyte population were downregulated in the IL-2 treatment phase. A decreasing trend or statistically significant attenuation of plasma IL-15 (e), CCL2 (f), CCL11 (g), CCL4 (h), FLT3LG (i) and TNF (j) was noted following IL-2 administration. MMSE scores were improved through the IL-2 treatment phase and returned toward baseline after discontinuation of the treatment (k). A trend toward improved CDR-SB was observed on day 120, compared to baseline (l). The changes in the average of ADAS-Cog scores were not significant through this 24-week study (m). Numbers shown represent the mean ± SE. Mean change from baseline was evaluated with paired t-tests. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. Treg: Regulatory T cells, IL-2: Interleukin-2, MMSE: Mini-Mental State Examination, CDR-SB: Clinical Dementia Rating Scale Sum of Boxes, ADAS-Cog: Alzheimer’s Disease Assessment Scale Cognitive Subscale, CCL: C–C motif ligand