Cancer stem cell targeted cancer vaccines
Inventors
Bergstein, Ivan • Brooks, Christopher • Cirrito, Thomas P.
Assignees
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Publication Number
US-10485858-B2
Publication Date
2019-11-26
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
Cancer stem cell targeted cancer vaccines are described for treating brain cancer, including glioma, by administering a pharmaceutical composition comprising peptide antigens. The composition includes an IL-13Rα2 peptide selected 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.
The disclosed concept targets cancer stem cells and tumor bulk by using antigens associated with shared expression. The background rationale states that cancer stem cells resist conventional bulk-targeting therapies, and that targeting both cancer stem cells and tumor bulk via shared antigens is therefore provided.
The disclosure specifies HLA-A2 restricted CTL epitopes for IL-13Rα2, EphA2, and survivin, and includes a T cell helper epitope from tetanus toxoid. The composition is formulated as an emulsion and excludes administering a peptide consisting of SEQ ID NO:7.
Immune modulators and adjuvants are described in combination with the emulsion-formulated peptide composition, including GM-CSF and imiquimod as a TLR7 agonist, together with an emulsifier such as Montanide ISA-51 in emulsion formulations. The disclosure also describes preferred peptide sequences and variants via SEQ ID NO selection, including IL-13Rα2 variants including SEQ ID NO:3.
Claims Coverage
The independent claims define three distinct method scopes for treating brain cancer using emulsion-formulated peptide antigens selected from defined SEQ ID NOs, with an explicit exclusion of a specific peptide sequence, and optional immunomodulatory agents. Across the independent claims, there are 4 primary peptide antigen elements, an emulsion formulation requirement, a specified exclusion, and immune modulators including GM-CSF and imiquimod.
Emulsion-formulated peptide vaccine for brain cancer with IL-13Rα2, EphA2, survivin, and tetanus toxoid while excluding SEQ ID NO:7
Administering to a human subject a pharmaceutical composition formulated as an emulsion comprising an IL-13Rα2 peptide selected 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.
Emulsion-formulated peptide vaccine plus immunomodulatory agents for brain cancer with exclusion of SEQ ID NO:7
Administering to a subject a first pharmaceutical composition formulated as an emulsion comprising an IL-13Rα2 peptide selected 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 administering one or more immunomodulatory agents; wherein the method does not comprise administering a peptide consisting of SEQ ID NO:7.
Three-composition regimen for brain cancer with GM-CSF and imiquimod while excluding SEQ ID NO:7
Administering to a subject (i) a first pharmaceutical composition formulated as an emulsion comprising an IL-13Rα2 peptide selected 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; (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.
Across the independent claims, the claimed treatment of brain cancer relies on defined peptide antigen inclusion, an emulsion formulation requirement, and an exclusion of a peptide consisting of SEQ ID NO:7. Additional independent scope is provided either by adding one or more immunomodulatory agents or by specifically administering GM-CSF and imiquimod as separate compositions.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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