Compositions and Methods for Identification of Membrane Targets for Enhancement of T cell Activity Against Cancer
AssigneeYale University
InventorsSidi Chen, Lupeng Ye, Jonathan Park, Matthew Dong, Ryan D. Chow
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Abstract
The present invention includes compositions and methods for identification of membrane targets for enhancement of T cell activity against a disease, disorder or condition, and/or enhancing T cell anti-tumor activity in a subject in need thereof. In some embodiments, the disease is cancer. In further embodiments, the cancer is glioblastoma (GBM) or breast cancer.
Claims31
A non-naturally occurring or engineered sgRNA library (mmSurf) targeting membrane-bound molecules, comprising a plurality of nucleic acids comprising at least one nucleotide sequence selected from the group consisting of SEQ ID NOs:
- 1-6,628.
A non-naturally occurring or engineered sgRNA library (mSURFEOME2) targeting membrane-bound molecules, comprising a plurality of nucleic acids comprising at least one nucleotide sequence selected from the group consisting of SEQ ID NOs:
- 7,837-64,747.
An AAV library (AAV-Surf) comprising a plurality of vectors, wherein each vector comprises an expression cassette for an sgRNA comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs:
- 1-6,628.
An AAV library (AAV-SURFEOME2) comprising a plurality of vectors, wherein each vector comprises an expression cassette for an sgRNA comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs:
- 7,837-64,747.
An AAV-CRISPR T cell vector for efficient gene editing and high-throughput screen in T cells comprising a first ITR, a second ITR, an antibiotic resistance sequence, two sleeping beauty (SB) IR/DR repeats, a first promoter, an sgRNA, a second promoter, a Thy1.1 selection marker, an SB100x transposase, and a poly A sequence.
A genetically modified cell, wherein at least one gene selected from the group consisting of Mgat5, Pdia3, Lag3, and Emp1 has been mutated in the cell.
A method of treating a disease, disorder, or condition in a subject in need thereof, the method comprising administering to the subject a genetically modified T cell wherein at least one gene selected from the group consisting of Mgat5, Pdia3, Lag3 and Emp1 has been mutated in the T cell.
-105. (canceled)
Dependencies are inferred from the claim text.