MUC16 specific chimeric antigen receptors and uses thereof
Inventors
Sabzevari, Helen • SHAH, Rutul R.
Assignees
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Publication Number
US-11319380-B2
Publication Date
2022-05-03
Expiration Date
Abstract
Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from an anti-MUC16 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders.
Core Innovation
The invention relates to MUC16-specific chimeric antigen receptor (CAR) constructs for cancer therapy, where the CAR comprises an antigen-binding portion and intracellular signaling. The CAR includes a polypeptide having the amino acid sequence of SEQ ID NO: 31, and is described with a stalk domain, a transmembrane domain, and CD3ζ signaling, with costimulatory domains including 4-1BB (CD137) or CD28.
The disclosure further describes a vectorized design that can include an engineered truncated epidermal growth factor receptor, including HER1t and/or HER1t-1, and safety/kill tags are described as truncated epidermal growth factor receptor variants and/or CD20 tags, including fusion using a T2A peptide. Cytokines are described as optionally co-expressed, including membrane-bound IL-15 or IL-12.
The disclosed system is described for use with engineered immune effector cells including T cells, NK cells, cytotoxic T lymphocytes (CTLs), and regulatory T cells. The text also describes delivery modalities including lentiviral, retroviral, and non-viral approaches, including a Sleeping Beauty (SB) transposon system, and gene switching approaches including an ecdysone-style gene switch (RHEOSWITCH).
Claims Coverage
The independent claims identified in the provided content are directed to two inventive features: an isolated nucleic acid encoding a CAR with a defined amino acid sequence, and a vector that encodes a truncated epidermal growth factor receptor, a cytokine, and that same CAR sequence.
Isolated CAR encoding SEQ ID NO: 31 polypeptide
An isolated nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a polypeptide having the amino acid sequence of SEQ ID NO: 31.
Vector with truncated epidermal growth factor receptor, cytokine, and SEQ ID NO: 31 CAR
A vector comprising a backbone and a nucleic acid encoding a truncated epidermal growth factor receptor comprising at least one of HER1t, HER1t-1, or a functional variant thereof, a cytokine, and a chimeric antigen receptor (CAR) comprising a polypeptide having the amino acid sequence of SEQ ID NO: 31.
Across the independent claims, coverage centers on a CAR polypeptide defined by amino acid sequence identity (SEQ ID NO: 31) and, in the vector claim, the combined encoding of a truncated epidermal growth factor receptor module together with a cytokine and the SEQ ID NO: 31 CAR.
Stated Advantages
Documented Applications
Therapeutic and functional activity of engineered CAR-based immune effector cells directed to MUC16, including tumor control in NSG ovarian cancer models as described in the document.
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