Compositions and methods for TCR reprogramming using fusion proteins

  • US 11,028,142 B2
  • Filed: 08/10/2020
  • Issued: 06/08/2021
  • Est. Priority Date: 05/18/2015
  • Status: Active Grant
First Claim
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1. 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 (i) an extracellular domain, (ii) a transmembrane domain, and (iii) a TCR intracellular domain comprising a stimulatory domain from an intracellular signaling domain; and

    (b) a murine, human or humanized scFv or single domain antibody comprising an antigen binding domain; and

    a pharmaceutically acceptable carrier;

    wherein the TCR subunit and the antigen binding domain are operatively linked;

    wherein the extracellular domain, the transmembrane domain and the intracellular signaling domain are derived from a single subunit, wherein the single subunit is CD3 epsilon or wherein the single subunit is CD3 gamma;

    wherein the extracellular domain comprises an extracellular domain of the single subunit;

    wherein the TFP functionally interacts with an endogenous TCR when expressed in a T cell; and

    wherein the T cell exhibits increased cytotoxicity to a human cell expressing an antigen that specifically interacts with the antigen binding domain compared to a T cell not containing the TFP.

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