ANTIBODY/T-CELL RECEPTOR CHIMERIC CONSTRUCTS AND USES THEREOF

1 - 27 . (canceled)

28 . An antibody-T cell receptor (TCR) chimeric molecule (abTCR) that specifically binds to a target antigen, comprising:

a) a first polypeptide chain, wherein the first polypeptide chain comprises i) a first antigen-binding domain comprising a V H antibody domain, ii) a first constant domain or a fragment thereof from an immunoglobulin, and iii) a first TCR domain (TCRD) comprising a first transmembrane domain of a first TCR subunit; and

b) a second polypeptide chain, wherein the second polypeptide chain comprises i) a second antigen-binding domain comprising a V L antibody domain, ii) a second constant domain or a fragment thereof from an immunoglobulin, and iii) a second TCRD comprising a second transmembrane domain of a second TCR subunit,

wherein the V H antibody domain and the V L antibody domain form an antigen-binding module that specifically binds the target antigen, wherein:

(i) the first TCR subunit is TCRα, and the second TCR subunit is TCRβ;

(ii) the first TCR subunit is TCRβ, and the second TCR subunit is TCRα;

(iii) the first TCR subunit is TCRγ, and the second TCR subunit is TCRδ; or

(iv) the first TCR subunit is TCRδ, and the second TCR subunit is TCRγ; and

wherein the first TCRD and the second TCRD form a TCR module (TCRM) that is capable of recruiting at least one TCR-associated signaling module.

29 . The abTCR of claim 28 , wherein the first and second constant domain or fragment thereof each comprises, independently, a CH1, CH2, CH3, CH4, or CL antibody domain or a fragment thereof.

30 . The abTCR of claim 29 , wherein:

(i) the first constant domain or fragment thereof comprises a CH1 antibody domain or a fragment thereof, and the second constant domain or fragment thereof comprises a CL antibody domain or a fragment thereof; or

(ii) the second constant domain or fragment thereof comprises a CH1 antibody domain or a fragment thereof, and the first constant domain or fragment thereof comprises a CL antibody domain or a fragment thereof.

31 . The abTCR of claim 28 , wherein:

i) the first TCRD further comprises a first connecting peptide or a fragment thereof of a TCR subunit N-terminal to the first transmembrane domain; and/or

ii) the second TCRD further comprises a second connecting peptide or a fragment thereof of a TCR subunit N-terminal to the second transmembrane domain.

32 . The abTCR of claim 28 , wherein:

i) the first TCRD further comprises a first TCR intracellular domain comprising a TCR intracellular sequence C-terminal to the first transmembrane domain; and/or

ii) the second TCRD further comprises a second TCR intracellular domain comprising a TCR intracellular sequence C-terminal to the second transmembrane domain.

33 . The abTCR of claim 28 , wherein:

i) the first polypeptide chain further comprises a first signaling peptide N-terminal to the first antigen-binding domain; and/or

ii) the second polypeptide chain further comprises a second signaling peptide N-terminal to the second antigen-binding domain.

34 . The abTCR of claim 28 , wherein:

i) the first polypeptide chain further comprises a first accessory intracellular domain comprising a co-stimulatory intracellular signaling sequence C-terminal to the first transmembrane domain; and/or

ii) the second polypeptide chain further comprises a second accessory intracellular domain comprising a co-stimulatory intracellular signaling sequence C-terminal to the second transmembrane domain.

35 . The abTCR of claim 28 , wherein the TCR-associated signaling module is selected from the group consisting of CD3δε, CD3γε, and ζζ.

36 . The abTCR of claim 28 , wherein the target antigen is a cell surface antigen.

37 . The abTCR of claim 36 , wherein the cell surface antigen is CD19, ROR1, ROR2, BCMA, GPRC5D, or FCRL5.

38 . The abTCR of claim 28 , wherein the target antigen is a complex comprising a peptide and a major histocompatibility complex (MHC) protein (a peptide/MHC complex).

39 . The abTCR of claim 38 , wherein the peptide in the peptide/MHC complex is derived from a protein selected from the group consisting of WT-1, AFP, HPV16-E7, NY-ESO-1, PRAME, EBV-LMP2A, HIV-1, and PSA.

40 . Nucleic acid(s) or vector(s) encoding the first and second polypeptide chains of the abTCR of claim 28 .

41 . An effector cell presenting on its surface the abTCR of claim 28 .

42 . The effector cell of claim 41 , wherein the effector cell is selected from the group consisting of a cytotoxic T cell, a helper T cell, a natural killer T cell, and a suppressor T cell.

43 . The effector cell of claim 41 , wherein the effector cell:

i) does not express the first TCR subunit and/or the second TCR subunit; or

ii) is modified to block or decrease endogenous expression of the first TCR subunit and/or the second TCR subunit.

44 . A method of killing a target cell presenting a target antigen, comprising contacting the target cell with the effector cell of claim 41 , wherein the abTCR specifically binds to the target antigen.

45 . A pharmaceutical composition comprising the effector cell of claim 41 , and a pharmaceutically acceptable carrier.

46 . A method of treating a target antigen-associated disease in an individual in need thereof, comprising administering to the individual an effective amount of the pharmaceutical composition of claim 45 , wherein the abTCR specifically binds to the target antigen.

47 . The method of claim 46 , wherein the target antigen-associated disease is a cancer.