CHIMERIC RECEPTORS AND USES THEREOF IN IMMUNE THERAPY

摘要

Disclosed herein are chimeric receptors comprising an extracellular domain with affinity and specific for the Fc portion of an immunoglobulin molecule (Ig) (e.g., an extracellular ligand-binding domain of F158 FCGR3A or V158 FCGR3A variant); a transmembrane domain (e.g., a transmembrane domain of CD8α); at least one co-stimulatory signaling domain (e.g., a co-stimulatory signaling domain of 4-1BB); and a cytoplasmic signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM) (e.g., a cytoplasmic signaling domain of CD3ζ). Also provided herein are nucleic acids encoding such chimeric receptors and immune cells expressing the chimeric receptors. Such immune cells can be used to enhance antibody-dependent cell-mediated cytotoxicity and/or to enhance antibody-based immunotherapy, such as cancer immunotherapy.

主权项

1. A chimeric receptor, comprising:
(a) an extracellular ligand-binding domain of an Fc receptor; (b) a transmembrane domain; (c) at least one co-stimulatory signaling domain; and (d) a cytoplasmic signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein either (c) or (d) is located at the C-terminus of the chimeric receptor; and wherein if (a) is an extracellular ligand-binding domain of CD16A, (d) does not comprise an ITAM domain of an Fc receptor.