Engineered T cells
AssigneesRegeneron Pharmaceuticals, Inc., Medigene Immunotherapies GmbH
InventorsJasdeep Mann, Christian Ellinger, Daniel Sommermeyer, Benjamin Boyerinas
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Abstract
The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.
Claims48
A method of treating a subject having a solid cancer, comprising administering to the subject an effective amount of a T cell comprising a first polynucleotide encoding a MAGEA4 TCR;
- and a second polynucleotide encoding a fusion polypeptide, wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO:
- 2 or 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO:
- 3 or 6, and wherein the fusion polypeptide comprises:
- (a) a first polypeptide comprising:
- (i) an extracellular TGFβ1-binding domain of TGFβR2;
- (ii) an IL-12Rβ2 transmembrane domain or an IL-12Rβ1 transmembrane domain;
- and
- (iii) an IL-12Rβ2 intracellular signaling domain or an IL-12Rβ1 intracellular signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- (i) an extracellular TGFβ1-binding domain of TGFβR1;
- (ii) an IL-12Rβ2 transmembrane domain or an IL-12Rβ1 transmembrane domain;
- and
- (iii) an IL-12Rβ2 intracellular signaling domain or an IL-12Rβ1 intracellular signaling domain.
A method of treating a subject having a solid cancer, comprising administering to the subject an effective amount of a T cell comprising a first polynucleotide encoding a MAGEA4 TCR;
- and a second polynucleotide encoding a fusion polypeptide, wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO:
- 2 or 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO:
- 3 or 6, and wherein the fusion polypeptide comprises:
- (a) a TGFβR2 polypeptide comprising:
- (i) an extracellular TGFβ1-binding domain of TGFβR2;
- (ii) an IL-12Rβ2 transmembrane domain;
- and
- (iii) an IL-12Rβ2 intracellular signaling domain;
- (b) a viral self-cleaving 2A peptide;
- and
- (c) a TGFβR1 polypeptide comprising:
- (i) an extracellular TGFβ1-binding domain of TGFβR1;
- (ii) an IL-12Rβ1 transmembrane domain;
- and
- (iii) an IL-12Rβ1 intracellular signaling domain.
A method of treating a subject having a solid cancer, comprising administering to the subject an effective amount of a T cell comprising a first polynucleotide encoding a MAGEA4 TCR;
- and a second polynucleotide encoding a fusion polypeptide, wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO:
- 2 or 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO:
- 3 or 6, and wherein the fusion polypeptide comprises:
- (a) a TGFβR2 polypeptide comprising:
- (i) an extracellular TGFβ1-binding domain of TGFβR2;
- (ii) an IL-12Rβ1 transmembrane domain;
- and
- (iii) an IL-12Rβ1 intracellular signaling domain;
- (b) a viral self-cleaving 2A peptide;
- and
- (c) a TGFβR1 polypeptide comprising:
- (i) an extracellular TGFβ1-binding domain of TGFβR1;
- (ii) an IL-12Rβ2 transmembrane domain;
- and
- (iii) an IL-12Rβ2 intracellular signaling domain.
A T cell comprising a first polynucleotide encoding a MAGEA4 TCR;
- and a second polynucleotide encoding a fusion polypeptide wherein the MAGEA4 TCR comprises an alpha chain comprising an amino acid sequence set forth in SEQ ID NO:
- 2 or 5 and a beta chain comprising an amino acid sequence set forth in SEQ ID NO:
- 3 or 6, and wherein the fusion polypeptide comprises SEQ ID NO:
- 8.
Dependencies are inferred from the claim text.