Compositions and methods for TCR reprogramming using fusion proteins
First Claim
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1. A pharmaceutical composition comprising(I) a T cell from a human subject, wherein the T cell comprises a recombinant nucleic acid molecule encoding a T cell receptor (TCR) fusion protein (TFP) comprising(a) a TCR subunit comprising a full-length CD3 epsilon sequence or a full-length CD3 gamma sequence;
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(II) a pharmaceutically acceptable carrier;
wherein the TCR subunit and the anti-BCMA binding domain are operatively linked;
wherein the TFP functionally interacts with an endogenous TCR when expressed in the T cell; and
wherein the T cell exhibits increased cytotoxicity to a cell expressing an antigen that specifically interacts with the anti-BCMA binding domain compared to a T cell not containing the TFP.
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Abstract
Provided herein are T-cell receptor (TCR) fusion proteins (TFPs), T-cells engineered to express one or more TFPs, and methods of use thereof for the treatment of diseases, including cancer.
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Citations
30 Claims
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1. A pharmaceutical composition comprising
(I) a T cell from a human subject, wherein the T cell comprises a recombinant nucleic acid molecule encoding a T cell receptor (TCR) fusion protein (TFP) comprising (a) a TCR subunit comprising a full-length CD3 epsilon sequence or a full-length CD3 gamma sequence; - and
(b) a mammalian scFv or single domain antibody comprising an anti-B-cell maturation antigen (BCMA) binding domain; and (II) a pharmaceutically acceptable carrier; wherein the TCR subunit and the anti-BCMA binding domain are operatively linked; wherein the TFP functionally interacts with an endogenous TCR when expressed in the T cell; and wherein the T cell exhibits increased cytotoxicity to a cell expressing an antigen that specifically interacts with the anti-BCMA binding domain compared to a T cell not containing the TFP. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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26. A pharmaceutical composition comprising
(I) a T cell from a human subject, wherein the T cell comprises a recombinant nucleic acid molecule encoding a T cell receptor (TCR) fusion protein (TFP) comprising (a) a TCR subunit comprising a full-length CD3 epsilon sequence or a full-length CD3 gamma sequence; - and
(b) a mammalian scFv or single domain antibody comprising an anti-BCMA binding domain; and (II) a pharmaceutically acceptable carrier; wherein the TCR subunit and the anti-BCMA binding domain are operatively linked; wherein the TFP functionally interacts with an endogenous TCR when expressed in the T cell; wherein the TFP lacks a costimulatory domain and lacks a heterologous stimulatory domain; and wherein the T cell exhibits increased cytotoxicity to a cell expressing an antigen that specifically interacts with the anti-BCMA binding domain compared to a T cell not containing the TFP. - View Dependent Claims (27, 28, 29, 30)
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Specification