TY - JOUR TI - A human antibody selective for transthyretin amyloid removes cardiac amyloid through phagocytic immune cells AU - Michalon, Aubin AU - Hagenbuch, Andreas AU - Huy, Christian AU - Varela, Evita AU - Combaluzier, Benoit AU - Damy, Thibaud AU - Suhr, Ole B. AU - Saraiva, Maria J. AU - Hock, Christoph AU - Nitsch, Roger M. AU - Jan Grimm T2 - Nature Communications AB - Transthyretin amyloid (ATTR) cardiomyopathy is a debilitating disease leading to heart failure and death. It is characterized by the deposition of extracellular ATTR fibrils in the myocardium. Reducing myocardial ATTR load is a therapeutic goal anticipated to translate into restored cardiac function and improved patient survival. For this purpose, 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. DA - 2021/05/25/ PY - 2021 DO - 10.1038/s41467-021-23274-x DP - www.nature.com VL - 12 IS - 1 SP - 3142 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-021-23274-x Y2 - 2021/05/25/16:53:16 ER -