Cancer vaccines targeting mesothelin and uses thereof
Inventors
Yan, Jian • SLAGER, Anna • GARMAN, Bradley • COOCH, Neil
Assignees
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Publication Number
US-11986517-B2
Publication Date
2024-05-21
Expiration Date
Abstract
Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a modified consensus mesothelin antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a modified consensus mesothelin antigen are disclosed. Methods of treating a subject with a mesothelin-expressing tumor and methods of preventing a mesothelin-expressing tumor are disclosed. Modified consensus mesothelin antigen is disclosed.
Core Innovation
The invention provides a modified synthetic consensus mesothelin antigen, SEQ ID NO: 2, and encoding DNA, SEQ ID NO: 1. The antigen exhibits 95.2% identity to human mesothelin and comprises Y303A to disrupt MUC16/CA125 binding, alongside S583T and T585V to disrupt GPI attachment. This consensus antigen is provided for vaccines targeting mesothelin-expressing cancers.
Preclinical studies indicate that vaccination induces antigen-specific CD4+ and CD8+ T-cell responses in mice, demonstrating stronger CD8+ cellular immune responses. In non-human primates, tested subjects develop IFNγ responses after mesothelin administration alone, whereas adding IL-12 demonstrates no significant overall improvement. The background problem being solved by the invention is not explicitly described in the provided patent disclosure.
Claims Coverage
The claim coverage includes three inventive features relating to protein sequences comprising the specified amino-acid region or full sequence of SEQ ID NO: 2, and identity-based variants with specified amino acids at positions 303, 583, and 585.
Protein comprising amino acids 19–607 of SEQ ID NO: 2
Claim 1 covers a protein comprising amino acids 19–607 of SEQ ID NO: 2, or a sequence at least 96% identical to that region, wherein the protein comprises alanine at position 303, threonine at position 583, and valine at position 585 relative to SEQ ID NO: 2.
Protein comprising SEQ ID NO: 2 or a variant
Claim 2 covers a protein comprising SEQ ID NO: 2, or a sequence at least 96% identical to SEQ ID NO: 2, wherein the protein comprises alanine at position 303, threonine at position 583, and valine at position 585 relative to SEQ ID NO: 2.
Protein comprising the amino acid sequence set forth in SEQ ID NO: 2
Claim 3 covers a protein comprising the amino acid sequence set forth in SEQ ID NO: 2.
The claims cover proteins comprising either the amino-acid region 19–607 or the full sequence of SEQ ID NO: 2, including specified identity-based variants, as well as a protein comprising SEQ ID NO: 2.
Stated Advantages
Not explicitly described in patent.
Documented Applications
The modified consensus mesothelin antigen is proposed for vaccines targeting mesothelin-expressing cancers.
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