A Humanized Monoclonal Antibody Against CD300A Ameliorates Acute Ischemic Stroke in Humanized Mice.

CD300a and CD300A, among the CD300 immunoglobulin (Ig)-like receptor family members in mice and humans, respectively, are expressed on myeloid cell lineage. The interaction of CD300a and CD300A with their ligands phosphatidylserine and phosphatidylethanolamine, respectively, exposed on the plasma membrane of dead cells mediate an inhibitory signal in myeloid cells. We previously reported that a neutralizing antimouse CD300a monoclonal antibody (mAb) enhanced efferocytosis by macrophages and ameliorated acute ischemic stroke (AIS) in mice. Unlike mouse CD300a, human CD300A has a single nucleotide polymorphism (SNP, rs2272111) encoding a nonsense mutation of glutamine (CD300A) instead of arginine (CD300A) at residue 111. In this study, we show that the SNP frequency is 32%-35% for the heterozygous allele and 4%-5% for the homozygous alleles, except Africa. In addition, we developed a humanized antihuman CD300A mAb, named TNAX103, that recognizes both CD300A and CD300A. We show that TNAX103 interfered with the binding of CD300A and CD300A to dead cells. In addition, the injection of TNAX103 decreased neurological scores and prolonged survival in humanized mice after middle cerebral artery occlusion. These results suggest that TNAX103 may be potentially useful for the treatment of patients expressing either CD300A or CD300A with AIS.