MUC16 specific chimeric antigen receptors and uses thereof
Inventors
Sabzevari, Helen • Shah, Rutul
Assignees
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Publication Number
US-11981746-B2
Publication Date
2024-05-14
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 disclosure relates to a nucleic acid encoding a chimeric antigen receptor and to immune effector cells comprising the chimeric antigen receptor. The chimeric antigen receptor comprises an antigen-binding domain, a transmembrane domain, and a cytoplasmic domain, and the antigen-binding domain comprises the amino acid sequence of SEQ ID NO: 5 and the amino acid sequence of SEQ ID NO: 6. The described engineered cell platform is framed as using the defined CAR architecture.
The disclosure also describes MUC16-specific chimeric antigen receptor constructs for cancer therapy. The CAR includes an antigen-binding domain comprising an anti-MUC16 monoclonal antibody scFv, with the CAR architecture further incorporating a transmembrane domain and a cytoplasmic domain. The cytoplasmic domain incorporates costimulatory signaling domains including 4-1BB and/or CD28, and includes a CD3ζ signaling domain.
The disclosure further describes engineered immune effector cells expressing the MUC16-specific CAR, including T cells, NK cells, cytotoxic T lymphocytes, and regulatory T cells, together with co-expression of cytokines and optional inducible gene-switch control. It also describes optional safety tag elements, including a truncated EGFR safety tag and/or a CD20 safety tag, and links kill tags using self-cleaving T2A.
Claims Coverage
The consolidated claim coverage identifies two independent claim themes: a nucleic acid encoding a chimeric antigen receptor and an immune effector cell comprising the chimeric antigen receptor. Across the independent claims, the coverage centers on a CAR core defined by an antigen-binding domain comprising SEQ ID NO: 5 and SEQ ID NO: 6, together with a transmembrane domain and a cytoplasmic domain.
Nucleic acid encoding a chimeric antigen receptor with defined antigen-binding domain
A nucleic acid encoding a chimeric antigen receptor, wherein the chimeric antigen receptor comprises an antigen-binding domain comprising the amino acid sequence of SEQ ID NO: 5 and the amino acid sequence of SEQ ID NO: 6, together with a transmembrane domain and a cytoplasmic domain.
Immune effector cell comprising a chimeric antigen receptor with defined antigen-binding domain
An immune effector cell comprising a chimeric antigen receptor comprising an antigen-binding domain comprising the amino acid sequence of SEQ ID NO: 5 and the amino acid sequence of SEQ ID NO: 6, together with a transmembrane domain and a cytoplasmic domain.
Overall, claim coverage is focused on a shared CAR core defined by SEQ ID NOs 5 and 6, together with a transmembrane domain and a cytoplasmic domain, implemented either as a nucleic acid encoding the CAR or as an immune effector cell expressing the CAR.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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