Methods and compositions relating to P62 for the treatment and prophylaxis of cancer
Inventors
Shneider, Alexander • Venanzi, Franco • Sherman, Michael • Shifrin, Victor
Assignees
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Publication Number
US-9717781-B2
Publication Date
2017-08-01
Expiration Date
Abstract
Provided herein are novel p62 compositions for the prophylaxis and treatment of cancer and related methods. The invention also provides modified p62 compositions that increase the anti-cancer activity of p62.
Core Innovation
The invention relates to p62/SQSTM1-based cancer vaccines. The cancer vaccine comprises a plasmid vector carrying a p62/SQSTM1 nucleic acid that encodes a polypeptide at least 98% identical to SEQ ID NO: 2, formulated in a pharmaceutically acceptable carrier. The vaccine stimulates the immune defense mechanism in a host to restrict spreading or progression of tumors or metastatic lesions.
The disclosure centers the therapeutic concept on combining the p62/SQSTM1-encoding cancer vaccine with a chemotherapeutic molecule. The chemotherapeutic molecule is selected from cyclophosphamide, doxorubicin, paclitaxel, docetaxel, vinblastin, methotrexate, navelbine, capecitabine, mitomycin C, and 5-fluorouracil. This combination is framed around restricting spreading or progression of tumors or metastatic lesions by engaging host immune defense mechanisms in addition to chemotherapy.
The document further describes refined vaccine compositions that incorporate additional genetic and immune-modulating components. Examples of refinement elements include nucleic acids encoding a fusion polypeptide, sequence motifs such as CpG stimulatory motifs, and nucleic acid targeting sequences directed to endocytic or ubiquitin-processing pathways. Delivery and immunomodulation elements are also described, including Marek’s disease virus type 1 VP22 sequences, mucosal delivery vectors, adjuvants, co-stimulatory components, and molecules that block suppressive or negative regulatory immune mechanisms.
Claims Coverage
The partial content identifies two independent claims (clm-00001 and clm-00011). Each independent claim requires a p62/SQSTM1 plasmid-vector cancer vaccine with a specified identity relationship to SEQ ID NO: 2, intended to stimulate immune defense to restrict tumor/metastatic lesion spreading or progression, combined with a chemotherapeutic molecule selected from a defined list.
P62/SQSTM1 plasmid-vector cancer vaccine with defined identity to SEQ ID NO: 2
A composition comprising a cancer vaccine comprising a plasmid vector comprising a p62/SQSTM1 nucleic acid that encodes a polypeptide at least 98% identical to SEQ ID NO: 2 in a pharmaceutically acceptable carrier, wherein the cancer vaccine stimulates the immune defense mechanism in a host to restrict spreading or progression of tumors or metastatic lesions.
Chemotherapeutic molecule selection for combination with p62/SQSTM1 vaccine
The composition further comprises a chemotherapeutic molecule selected from the group consisting of cyclophosphamide, doxorubicin, paclitaxel, docetaxel, vinblastin, methotrexate, navelbine, capecitabine, mitomycin C, and 5-fluorouracil.
Across both independent claims, the core claim coverage is the combination of a p62/SQSTM1 plasmid-vector cancer vaccine encoding a polypeptide defined by identity to SEQ ID NO: 2 and a chemotherapeutic molecule selected from the specified group, with the shared functional intent of stimulating host immune defense to restrict tumor or metastatic lesion spreading or progression.
Stated Advantages
Stimulates the immune defense mechanism in a host to restrict spreading or progression of tumors or metastatic lesions.
Documented Applications
Not explicitly described in patent.
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