Novel chimeric antigen receptors and libraries
AssigneeMassachusetts Institute of Technology
InventorsMichael Birnbaum, Taeyoon Kyung
Life of this patent
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Abstract
Provided herein are chimeric antigen receptor (CAR) viral libraries and methods of making the same. In some embodiments, the CAR comprises an intracellular domain (ICD) with at least one immune activation signaling domain, one co-stimulatory domain, and one or more inhibitory signaling domain or signaling domain from non-T cell lineages. In some embodiments, the signaling domains of the ICD are joined by distinct linkers of 10 amino acids. In some embodiments, the CARs contain a 18-nucleotide barcode in the 3′ untranslated region. Also provided herein, are CAR cell libraries and methods of making the same.
Claims25
1-39. (canceled)
A CAR, comprising:
- i) an extracellular domain;
- ii) a transmembrane domain;
- and
- iii) at least a first intracellular domain (ICD) and a second ICD,
- wherein, the first ICD is linked to the second ICD by a linker comprising at least 10 amino acids.
(canceled)
43-45. (canceled)
A polypeptide, comprising an amino acid sequence wherein the amino acid sequence has at least 70%, at least 80%, at least 85%, at least 90%, or at least 99% sequence identity to any one of SEQ ID NOs:4, 6, or 8 or to any one of SEQ ID NOs:4, 6, or 8 without an amino acid sequence comprising a myc-tag.
47-48. (canceled)
A CAR, comprising:
- an extracellular domain;
- a transmembrane domain;
- and an intracellular domain (ICD) comprised of three linked modules, wherein the three linked modules are any one of CD40-CD3zITAM3-DAP12, FCER1G-2B4-CD3zITAM3, or FCER1G-OX40-CD3zITAM.
51-52. (canceled)
A CAR, comprising:
- an extracellular domain;
- a transmembrane domain;
- and an intracellular domain (ICD) comprised of three linked modules, wherein the three linked modules are any one of CD40-CD3eITAM-DAP12 FCER1G-2B4-CD3eITAM, FCER1G-OX40-CD3zITAM3, PILRB-FCER1G-CD3zITAM3, CD3zITAM3-CD3d-CD4, or CD79a-CD79aITAM-CD4.
54-58. (canceled)
A CAR, comprising:
- an extracellular domain;
- a transmembrane domain;
- and at least a first intracellular domain (ICD) and a second ICD, wherein, the first ICD is linked to the second ICD by a linker comprising at least 10 amino acids.
Dependencies are inferred from the claim text.