Table 3.

Partial successes in antigen-specific prevention and intervention in humans: lessons learned

Trial	Treatment	Results	Lessons learned	Ref.
Oral insulin (DPT-1)	Secondary prevention in high-risk individuals with autoantibodies (372 treated subjects)	No prevention, except in a subgroup of patients with highest insulin autoantibody levels where loss of C-peptide was delayed	Unlike in NOD mice, proinsulin may not be a driving antigen in all patients; selecting antigens based on strong evidence of autoreactivity may be required	75,76
Proinsulin DNA (BHT-3021)	Phase 1 study in T1D patients with 5 years of onset and with residual C-peptide, involving intramuscular delivery of proinsulin-encoding plasmid (80 T1D patients)	Significant delay in C-peptide loss up to 15 weeks after treatment with 1-mg dose; significant decrease of proinsulin-reactive CD8+ T cells in treated HLA-A3+ patients	Presentation of proinsulin-derived peptides (at least HLA-A3 restricted) may mediate peripheral deletion of some autoreactive CD8+ T cells and delay CD8+ T cell–mediated β-cell destruction	77
GAD65-Alum (DIAGNODE-1)	Ongoing pilot study involving intralymphatic delivery of GAD65-alum and oral vitamin D (6 new-onset patients, all with GAD65 autoantibodies)	Promising results of C-peptide preservation relative to historical studies with GAD65-alum or anti-CD3; these data remain very preliminary	Intralymphatic delivery may provide better exposure of antigens and leverage nonmigratory subsets of APCs	78

DIAGNODE-1, GAD-Alum (Diamyd) Administered into Lymph Nodes in Combination with Vitamin D in Type 1 Diabetes; DPT-1, Diabetes Prevention Trial–Type 1 Diabetes.