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A human antibody selective for transthyretin amyloid removes cardiac amyloid through phagocytic immune cells
Aubin Michalon 1, Andreas Hagenbuch 2, Christian Huy 2, Evita Varela 2, Benoit Combaluzier 2, Thibaud Damy 3, Ole B Suhr 4, Maria J Saraiva 5, Christoph Hock 2 6, Roger M Nitsch 2 6, Jan Grimm 2
...we developed the selective anti-ATTR antibody NI301A, a recombinant human monoclonal immunoglobulin G1. NI301A was cloned following comprehensive analyses of memory B cell repertoires derived from healthy elderly subjects. NI301A binds selectively with high affinity to the disease-associated ATTR aggregates of either wild-type or variant ATTR related to sporadic or hereditary disease, respectively. It does not bind physiological transthyretin. NI301A removes ATTR deposits ex vivo from patient-derived myocardium by macrophages, as well as in vivo from mice grafted with patient-derived ATTR fibrils in a dose- and time-dependent fashion. The biological activity of ATTR removal involves antibody-mediated activation of phagocytic immune cells including macrophages. These data support the evaluation of safety and tolerability of NI301A in an ongoing phase 1 clinical trial in patients with ATTR cardiomyopathy.