1. Clinical Trial Arm
2. Genetic Edit Switchboard
HLA-I / HLA-II Knockout (Blocks CD8/CD4 TCR)
CD47 "Don't-Eat-Me" Overexpression (SIRPĪ±+ Blocks Macrophages & NKs)
PD-L1 Checkpoint Upregulation (Exhausts residual T-cells)
Systemic Immunosuppression (Tacrolimus/MMF)
Live Cellular Microenvironment
Interactive Graft Site: Click to Infuse Host Immune Cells
Engrafted Islet Cluster
Host CD8+ T-Cell
Missing-Self NK Cell
SIRPĪ± Macrophage
C-Peptide Secretion
[0.0m] System initialized. Engrafting allogeneic gene-edited islets into vascularized intramuscular site.
[0.0m] HLA Class I/II disruption prevents TCR allorecognition.
[0.0m] CD47 overexpression binds SIRPĪ± to prevent missing-self NK lysis & macrophage phagocytosis.
[14.0m] Graft fully viable. Robust insulin-independence confirmed.
[0.0m] HLA Class I/II disruption prevents TCR allorecognition.
[0.0m] CD47 overexpression binds SIRPĪ± to prevent missing-self NK lysis & macrophage phagocytosis.
[14.0m] Graft fully viable. Robust insulin-independence confirmed.
3. 14-Month Clinical Telemetry
Fasting C-Peptide
1.82 ng/mL
Baseline: 0.02 (Endogenous Ī²-cell func)
HbA1c Target
5.6%
Baseline: 8.4% (T1D Euglycemia)
Daily Exogenous Insulin
0.0 U/day
Baseline: 46 U/day (Complete Wean)
Graft Viability
98.4%
Histological Ī²-mass score
Biochemical Mechanism Insights
The "Missing-Self" NK Paradox: Stripping HLA-I eliminates alloreactive CD8+ T-cell attacks, but normally unleashes Natural Killer (NK) lysis via missing inhibitory KIR signals. Overexpressing CD47 triggers SIRPĪ± inhibitory cascades, shielding the graft from both NK cells and host macrophages.
PD-L1 Synergism: Directly engages PD-1 on lingering activated host lymphocytes, inducing immune tolerance and exhaustion without systemic toxicity.