(Macomics) Discovery of MACO355: a first in mechanism ligand-blocking independent LILRB1/2/3 antibody for cancer therapy

Introduction

Macrophages populate most solid tumors in large numbers and limit effective anti-tumoral immune responses ^[1]. The immunoreceptor tyrosine-based inhibitory motifs (‘ITIMs’)containing leukocyte immunoglobulin-like receptors (LILR) B1 and LILRB2 are expressed on tumor associated macrophages ^[2]. Despite sharing multiple ligands such as major histocompatibility complex class I G (HLA-G), LILRB1 regulates phagocytosis, whereas blocking ofLILRB2 ligand binding was shown to enhance cytokine release ^[3]. To date, therapeutic approaches to targeting LILRB1 and LILRB2 have blocked receptor – ligand interactions to relieve ligand-mediated immune suppression. To obtain antibodies with novel and superior LILRB1/LILRB2 modulating activity, we investigated both ligand blocking and non ligand-blocking clones.