T cells and chimeric stimulating receptors and uses thereof
AssigneeEureka Therapeutics, Inc.
InventorsCheng Liu, Hongbing Zhang, Zhiyuan Yang, Pengbo Zhang, Yixiang Xu, Guangyuan Xiong, Ziyou Cui
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Abstract
Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).
Claims71
An immune cell comprising:
- (a) an αβ T-cell receptor (TCR), and
- (b) a chimeric stimulating receptor (CSR) comprising:
- (i) a ligand-binding module that is capable of binding or interacting with a target ligand;
- (ii) a transmembrane domain (a CSR transmembrane domain);
- and
- (iii) a CD30 costimulatory domain,
- wherein the CSR lacks a functional primary signaling domain derived from the intracellular signaling sequence of CD3ζ, optionally wherein:
- the CD30 costimulatory domain comprises a sequence that can bind to an intracellular TRAF signaling protein, e.g., corresponding to residues 561-573 or 578-586 of a full-length CD30 having the sequence of SEQ ID NO:228;
- and/or
- the CD30 costimulatory domain comprises a sequence that is at least 80%, 85, 90%, 95%, or 100% identical to residues 561-573 or 578-586 of SEQ ID NO:228 or a sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to the sequence of SEQ ID NO:238.
A method of treating a solid tumor cancer in a subject, the method comprising the steps of:
- (a) transducing tumor infiltrating T cells (TIL T cells) obtained from the subject, or progenies of the TIL T cells, with a nucleic acid encoding, or a vector comprising a nucleic acid encoding, a chimeric stimulating receptor (CSR) comprising:
- (i) a ligand-binding module that is capable of binding or interacting with a target ligand;
- (ii) a transmembrane domain (a CSR transmembrane domain);
- and
- (iii) a CD30 costimulatory domain,
- wherein the CSR lacks a functional primary signaling domain;
- and
- (b) administering to the subject transduced TIL T cells or progenies thereof.
Dependencies are inferred from the claim text.