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.
Claims18
A method of killing a target cell presenting a target antigen, comprising contacting the target cell with an effector αβ T cell comprising an antibody-T cell receptor (TCR) chimeric molecule (abTCR) that specifically binds to the target antigen, wherein the abTCR comprises:
- a) a first polypeptide chain comprising a first antigen-binding domain comprising a VH antibody domain and a CH1 antibody domain, and a first T cell receptor domain (TCRD) comprising a first transmembrane domain of a first TCR subunit, wherein the first polypeptide chain lacks variable and constant domains of the first TCR subunit;
- and
- b) a second polypeptide chain comprising a second antigen-binding domain comprising a VL antibody domain and a CL antibody domain, and a second TCRD comprising a second transmembrane domain of a second TCR subunit, wherein the second polypeptide chain lacks variable and constant domains of the second TCR subunit,
- wherein the VH domain of the first antigen-binding domain pairs with the VL domain of the second antigen-binding domain to form an antigen-binding module that specifically binds to the target antigen,
- 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, and
- wherein the first TCR subunit is a TCR γ chain and the second TCR subunit is a TCR δ chain, or the first TCR subunit is a TCR δ chain and the second TCR subunit is a TCR γ chain.
A method of treating a target antigen-associated disease in an individual in need thereof comprising administering to the individual an effective amount of a composition comprising an effector αβ T cell comprising an abTCR that specifically binds to the target antigen, wherein the abTCR comprises:
- a) a first polypeptide chain comprising a first antigen-binding domain comprising a VH antibody domain and a CH1 antibody domain, and a first TCRD comprising a first transmembrane domain of a first TCR subunit, wherein the first polypeptide chain lacks variable and constant domains of the first TCR subunit;
- and
- b) a second polypeptide chain comprising a second antigen-binding domain comprising a VL antibody domain and a CL antibody domain, and a second TCRD comprising a second transmembrane domain of a second TCR subunit, wherein the second polypeptide chain lacks variable and constant domains of the second TCR subunit,
- wherein the VH domain of the first antigen-binding domain pairs with the VL domain of the second antigen-binding domain to form an antigen-binding module that specifically binds to the target antigen,
- 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, and
- wherein the first TCR subunit is a TCR γ chain and the second TCR subunit is a TCR δ chain, or the first TCR subunit is a TCR δ chain and the second TCR subunit is a TCR γ chain.
Dependencies are inferred from the claim text.