Antibody/T-cell receptor chimeric constructs and uses thereof
AssigneeEureka Therapeutics, Inc.
InventorsJingwei Lu, Zhiyuan Yang, Cheng Liu, Hong Liu, Yiyang Xu, Su Yan, Vivien Wai-Fan Chan, Lucas Horan
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Abstract
The present application provides antibody-TCR chimeric constructs comprising an antibody moiety that specifically binds to a target antigen fused to a TCRM capable of recruiting at least one TCR-associated signaling module. Also provided are methods of making and using these constructs.
Claims46
An antibody-T cell receptor (TCR) chimeric molecule (abTCR) that specifically binds to CD19, comprising:
- a) a first polypeptide chain comprising a first antigen-binding domain comprising VH and CH1 antibody domains and a first T cell receptor domain (TCRD) comprising a first transmembrane domain of a first TCR subunit;
- and
- b) a second polypeptide chain comprising a second antigen-binding domain comprising VL and CL antibody domains and a second TCRD comprising a second transmembrane domain of a second TCR subunit,
- wherein the VH and CH1 domains of the first antigen-binding domain and the VL and CL domains of the second antigen-binding domain form an antigen-binding module that specifically binds to CD19,
- wherein the first TCRD and the second TCRD form a T cell receptor module (TCRM) that is capable of recruiting at least one TCR-associated signaling module,
- wherein i) the first TCR subunit is a TCR γ chain, and the second TCR subunit is a TCR δ chain, or ii) the first TCR subunit is a TCR δ chain, and the second TCR subunit is a TCR γ chain,
- wherein the CH1 antibody domain comprises the amino acid sequence of SEQ ID NO:
- 39 and the CL antibody domain comprises the amino acid sequence of SEQ ID NO:
- 41,
- and wherein the VH antibody domain comprises the amino acid sequence of SEQ ID NO:
- 59 and the VL antibody domain comprises the amino acid sequence of SEQ ID NO:
- 57.
An antibody-T cell receptor (TCR) chimeric molecule (abTCR) that specifically binds to a complex comprising an AFP peptide and a major histocompatibility complex (MHC) protein, comprising:
- a) a first polypeptide chain comprising a first antigen-binding domain comprising Vu and CH1 antibody domains and a first T cell receptor domain (TCRD) comprising a first transmembrane domain of a first TCR subunit;
- and
- b) a second polypeptide chain comprising a second antigen-binding domain comprising VL and CL antibody domains and a second TCRD comprising a second transmembrane domain of a second TCR subunit,
- wherein the VH and CH1 domains of the first antigen-binding domain and the VL and CL domains of the second antigen-binding domain form an antigen-binding module that specifically binds to the complex comprising the AFP peptide and the MHC protein,
- wherein the first TCRD and the second TCRD form a T cell receptor module (TCRM) that is capable of recruiting at least one TCR-associated signaling module,
- wherein i) the first TCR subunit is a TCR γ chain, and the second TCR subunit is a TCR δ chain, or ii) the first TCR subunit is a TCR δ chain, and the second TCR subunit is a TCR γ chain, wherein the CH1 antibody domain comprises the amino acid sequence of SEQ ID NO:
- 39 and the CL antibody domain comprises the amino acid sequence of SEQ ID NO:
- 41,
- and wherein the VH antibody domain comprises the amino acid sequence of SEQ ID NO:
- 38 and the VL antibody domain comprises the amino acid sequence of SEQ ID NO:
- 40.
Dependencies are inferred from the claim text.