Cancer stem cell targeted cancer vaccines
Inventors
Bergstein, Ivan • Brooks, Christopher • Cirrito, Thomas P.
Assignees
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Publication Number
US-11672847-B2
Publication Date
2023-06-13
Expiration Date
Abstract
Provided herein are cancer stem cell targeted cancer vaccines and methods for treating and vaccinating against cancer. Also contained herein are regimens by which cancer stem cell targeted cancer vaccines are administered, such regimens comprising peptides, compositions, immunomodulatory agents, and emulsifiers. Also provided are the patient populations to which the regimens are to be administered, and the dosages, schedules, route of administration for the regimens.
Core Innovation
The invention relates to peptide-based cancer stem cell targeted cancer vaccines for treating brain cancer in a human subject. The pharmaceutical composition includes an IL-13Rβ2 peptide with an amino acid sequence chosen from SEQ ID NOs:1-4, an EphA2 peptide having the amino acid sequence set forth in SEQ ID NO:5, a survivin peptide having the amino acid sequence set forth in SEQ ID NO:9, and a Tetanus toxoid peptide having the amino acid sequence set forth in SEQ ID NO:10. The composition is formulated as an emulsion and is administered in combination with bevacizumab.
The invention addresses the problem of treating brain cancer by targeting both cancer stem cells and tumor bulk cells using defined antigenic peptides. The disclosed cancer stem cell marker includes CD133, and the document indicates that relevant cancer cells co-express EphA2 and IL-13Rβ2, supporting these antigens as cancer stem cell targets. The vaccine formulation explicitly does not comprise administering a peptide consisting of SEQ ID NO:7.
The invention further includes use of immunomodulatory agents and delivery as an emulsion. The partial content identifies immunomodulatory agents/adjuvants including GM-CSF and imiquimod, and describes immunomodulatory agent use in conjunction with emulsion delivery using Montanide ISA-51. The combination is presented for administering a pharmaceutical composition comprising the peptide emulsion plus immunomodulatory agents, in a regimen involving co-administration with bevacizumab.
Claims Coverage
Independent claims are directed to treating brain cancer in a human subject using an emulsion-formulated multi-peptide composition and co-administration with bevacizumab, with explicit exclusion of a survivin peptide consisting of SEQ ID NO:7. The independent claims each incorporate distinct additional inventive features: inclusion/exclusion of particular peptides, addition of immunomodulatory agents, and separation into first/second/third pharmaceutical compositions with defined components (including GM-CSF and imiquimod).
Emulsion multi-peptide composition with bevacizumab co-administration excluding SEQ ID NO:7
Administering an emulsion pharmaceutical composition comprising an IL-13Rβ2 peptide chosen from SEQ ID NOs:1-4, an EphA2 peptide set forth in SEQ ID NO:5, a survivin peptide set forth in SEQ ID NO:9, and a Tetanus toxoid peptide set forth in SEQ ID NO:10, wherein the method does not comprise administering a peptide consisting of SEQ ID NO:7, and wherein the pharmaceutical composition is co-administered with bevacizumab.
Emulsion multi-peptide composition plus one or more immunomodulatory agents excluding SEQ ID NO:7 and co-administration with bevacizumab
Administering (i) an emulsion pharmaceutical composition comprising an IL-13Rβ2 peptide chosen from SEQ ID NOs:1-4, an EphA2 peptide set forth in SEQ ID NO:5, a survivin peptide set forth in SEQ ID NO:9, and a Tetanus toxoid peptide set forth in SEQ ID NO:10, and (ii) one or more immunomodulatory agents, wherein the method does not comprise administering a peptide consisting of SEQ ID NO:7, and wherein the pharmaceutical composition is co-administered with bevacizumab.
Three composition regimen: emulsion peptides, GM-CSF, and imiquimod with bevacizumab excluding SEQ ID NO:7
Administering (i) a first pharmaceutical composition comprising an IL-13Rβ2 peptide chosen from SEQ ID NOs:1-4, an EphA2 peptide set forth in SEQ ID NO:5, a survivin peptide set forth in SEQ ID NO:9, and a Tetanus toxoid peptide set forth in SEQ ID NO:10, wherein said composition is formulated as an emulsion; (ii) a second pharmaceutical composition comprising GM-CSF; and (iii) a third pharmaceutical composition comprising imiquimod, wherein the method does not comprise administering a peptide consisting of SEQ ID NO:7, and wherein the pharmaceutical composition is co-administered with bevacizumab.
Across the independent claims, the core inventive coverage centers on treating brain cancer by administering an emulsion-formulated pharmaceutical composition containing IL-13Rβ2, EphA2, survivin, and Tetanus toxoid peptides, with explicit exclusion of a peptide consisting of SEQ ID NO:7 and co-administration with bevacizumab. Additional independent-claim differentiation is achieved by adding one or more immunomodulatory agents or by specifying separate pharmaceutical compositions that include GM-CSF and imiquimod.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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