Yeast-brachyury immunotherapeutic compositions
Inventors
Palena, Claudia • Guo, Zhimin • Apelian, David • Schlom, Jeffrey
Assignees
GlobeImmune Inc • US Department of Health and Human Services
Publication Number
US-9623097-B2
Publication Date
2017-04-18
Expiration Date
2032-03-19
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Abstract
Disclosed are yeast-based immunotherapeutic compositions comprising Brachyury antigens, and methods for the prevention and/or treatment of cancers characterized by the expression or overexpression of Brachyury.
Core Innovation
The invention relates to yeast-based immunotherapeutic compositions comprising Brachyury antigens and methods for preventing and/or treating cancers characterized by the expression or overexpression of Brachyury. These compositions use a yeast vehicle expressing at least one Brachyury antigen or immunogenic domain thereof to elicit a Brachyury-specific cellular immune response including CD4+ and CD8+ T cells, which can reduce tumor burden, inhibit tumor growth, increase survival, and prevent or inhibit metastatic progression of cancer.
Brachyury is a mesodermal transcription factor involved in the epithelial-mesenchymal transition (EMT) and metastatic progression of cancers. It is expressed in a variety of human tumors and cancer cell lines, including late-stage, metastatic, and B cell-origin cancers. Existing cancer therapies have limitations in treating metastatic and resistant cancers expressing Brachyury, creating a need for novel immunotherapeutic compositions to effectively treat or prevent these cancers.
The invention addresses this need by providing yeast-Brachyury immunotherapeutics that can be used prophylactically or therapeutically to prevent, inhibit, delay, arrest, or reverse metastatic progression in individuals with or at risk of Brachyury-expressing cancers. These compositions can be administered alone or in combination with other therapies, such as chemotherapy, radiation, or other immunotherapies, to enhance treatment effectiveness, including reduction of chemotherapy and radiation resistance.
Claims Coverage
The patent includes one independent claim detailing a method involving a yeast-based immunotherapeutic composition expressing a Brachyury fusion protein.
Method of treating cancer with a yeast-based immunotherapeutic composition
Administering to an individual a composition comprising a whole, inactivated yeast expressing a Brachyury fusion protein consisting of amino acids 2-435 of SEQ ID NO:6 or SEQ ID NO:18, eliciting a Brachyury-specific T cell response to reduce tumor burden, increase survival, or inhibit tumor growth.
Combination with surgical resection and other therapies
The method may further comprise surgical resection of a tumor and/or administration of additional therapies including chemotherapy, targeted cancer therapy, radiation therapy, adoptive T cell transfer, or other immunotherapeutic compositions comprising additional cancer antigens that do not include Brachyury.
Use of specific Brachyury fusion proteins and yeast strains
Using Brachyury fusion proteins with sequences corresponding to positions 2-435 of SEQ ID NO:6 or SEQ ID NO:18, or sequences SEQ ID NO:8 or SEQ ID NO:20, expressed by whole, heat-inactivated yeast, preferably Saccharomyces cerevisiae.
The claims cover a method of treating cancer using inactivated yeast expressing specific Brachyury fusion proteins, alone or combined with other cancer therapies or immunotherapy compositions targeting additional cancer antigens, with specificity for whole, heat-inactivated yeast, especially Saccharomyces cerevisiae.
Stated Advantages
Yeast-Brachyury immunotherapeutic compositions effectively target metastatic and late-stage cancers associated with Brachyury expression.
They reduce or eliminate chemotherapy and radiation resistance in metastatic cancer, thereby enhancing existing cancer therapies.
They induce potent cellular immune responses, including CD4+ and CD8+ T cells, without exogenous adjuvants or immunostimulatory molecules, minimizing toxicity.
They can be used prophylactically in healthy or high-risk individuals to prevent or delay onset of Brachyury-expressing cancers.
The immunotherapy can be personalized and combined with other immunotherapeutic compositions targeting additional cancer antigens for improved efficacy.
Documented Applications
Prevention and treatment of cancers expressing or overexpressing Brachyury, including metastatic and late-stage cancers of epithelial origin such as breast, small intestine, stomach, pancreatic, kidney, bladder, uterine, ovarian, testicular, lung, colon, and prostate cancers.
Treatment of B cell-origin tumors expressing Brachyury, including chronic lymphocytic leukemia, Epstein-Barr virus transformed B cells, Burkitt's lymphoma, Hodgkin's lymphoma, and metastatic cancers thereof.
Use as an adjunct to chemotherapy and radiation therapy to reduce or prevent therapy resistance in patients receiving such treatments.
Potential treatment or prevention of diseases or conditions associated with infectious agents, including viral infections such as Epstein Barr Virus (EBV).
Use in cancer patients in combination with other immunotherapeutic compositions or cancer therapies, including surgical tumor resection, chemotherapy, targeted therapy, radiation, and adoptive T cell transfer.
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