LEAPS heteroconjugate is able to prevent and treat experimental autoimmune myocarditis by altering trafficking of autoaggressive cells to the heart

D Cihakova, JG Barin, GC Baldeviano, M Kimura… - International …, 2008 - Elsevier
D Cihakova, JG Barin, GC Baldeviano, M Kimura, MV Talor, DH Zimmerman, E Talor…
International immunopharmacology, 2008Elsevier
We evaluated the efficacy of the Ligand Epitope Antigen Presentation System (LEAPS™) in
preventing or treating experimental autoimmune myocarditis (EAM) in A/J mice. LEAPS
(here, J-My-1) is a conjugate of the myocarditogenic peptide of cardiac myosin MyHCα334–
352 (My-1) and J peptide, derived from the sequence of human β-2 microglobulin.
Remarkably, early prophylactic (J-My-1 injected on days− 14 and− 7 before EAM induction),
late prophylactic (J-My-1 injected on days 0, 7, 14, and 21), and therapeutic (J-My-1 injected …
We evaluated the efficacy of the Ligand Epitope Antigen Presentation System (L.E.A.P.S.™) in preventing or treating experimental autoimmune myocarditis (EAM) in A/J mice. L.E.A.P.S. (here, J-My-1) is a conjugate of the myocarditogenic peptide of cardiac myosin MyHCα334–352 (My-1) and J peptide, derived from the sequence of human β-2 microglobulin. Remarkably, early prophylactic (J-My-1 injected on days −14 and −7 before EAM induction), late prophylactic (J-My-1 injected on days 0, 7, 14, and 21), and therapeutic (J-My-1 injected on days 7, 14, and 21 or 10, 17 and 24) administration of J-My-1 significantly decreased the incidence and severity of EAM. However, extended therapeutic treatment was associated with anaphylaxis and death, corresponding with global immune activation associated with J-My-1 treatment. In J-My1-treated animals, we observed expanded numbers of activated CD69+ and CD44+ CD4+ and CD8+ T cells in the spleens. J-My-1 treatment also increased the proportion of CD11c+ dendritic cells in spleens and induced strong production of anti-J-My-1 specific antibodies. J-My-1 injections resulted in decreased levels of chemokines MIP-1α and IP-10 in hearts. We propose that J-My-1 treatment interferes with trafficking of autoaggressive immune cells to the heart.
Elsevier