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-11944673-B2
Publication Date
2024-04-02
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 the prevention and/or treatment of cancers characterized by the expression or overexpression of Brachyury. These compositions typically include a yeast vehicle and at least one Brachyury antigen, often expressed as a recombinant protein by the yeast. The invention encompasses both prophylactic and therapeutic uses of these compositions, targeting cancer cells expressing Brachyury, including metastatic and late-stage cancers, as well as pre-cancerous lesions and individuals at high risk.
Brachyury is a mesodermal transcription factor involved in early development and epithelial-mesenchymal transition (EMT) in human tumor cells, which confers migratory, invasive abilities and contributes to metastatic progression of cancer. Conventional cancer therapies have limited success in treating metastatic cancers or cancers associated with Brachyury expression. Therefore, there remains a need for effective immunotherapeutic products that target Brachyury-expressing cancers. The yeast-based immunotherapeutic compositions presented provide a novel approach by generating Brachyury-specific cellular immune responses, including CD4+ and CD8+ T cell responses, capable of preventing, treating, delaying, inhibiting, or reversing metastatic cancer progression and improving outcomes.
The yeast-Brachyury immunotherapy compositions can also be used to prevent or reduce chemotherapy-resistance or radiation-resistance in metastatic cancers by inhibiting Brachyury expression and may enhance the efficacy of these therapies. Additionally, they can be combined with other immunotherapeutic compositions targeting different cancer antigens or with other cancer treatments. The compositions stimulate innate and adaptive immune responses without need for exogenous adjuvants or cytokines and modulate regulatory T cell functionality to enhance effector responses.
Claims Coverage
The claims include one independent claim focused on a method to prevent or delay Brachyury-expressing cancer onset in an at-risk individual with a pre-cancerous lesion using a yeast-based immunotherapeutic composition.
Method to prevent or delay onset of Brachyury-expressing cancer in individuals with pre-cancerous lesions
Administering to an individual at risk of metastatic progression and having a pre-cancerous lesion an immunotherapeutic composition comprising: (a) a yeast vehicle; and (b) a cancer antigen comprising a Brachyury antigen that includes SEQ ID NO:6, positions 2-435 of SEQ ID NO:6, SEQ ID NO:18, or positions 2-435 of SEQ ID NO:18.
The independent claim covers a method of preventing or delaying Brachyury-expressing cancer by administering a yeast-based immunotherapeutic composition containing specified Brachyury antigens to at-risk individuals with pre-cancerous lesions.
Stated Advantages
Effectively targets tumor cells expressing or overexpressing Brachyury, including late-stage and metastatic cancers.
Generates potent Brachyury-specific cellular immune responses (CD4+ and CD8+ T cells) without exogenous adjuvants or cytokines.
Inhibits metastatic progression of cancer by targeting EMT-associated Brachyury.
Can reduce or prevent chemotherapy and radiation resistance in tumor cells.
Adaptable for combination with other immunotherapeutic cancer treatments and cancer antigens.
Capable of repeated administration without loss of efficacy.
Documented Applications
Prevention or treatment of cancers characterized by expression or overexpression of Brachyury including breast, small intestine, stomach, kidney, bladder, uterus, ovary, testes, lung, colon, pancreas, prostate cancers, and B cell origin tumors like chronic lymphocytic leukemia, Burkitt's and Hodgkin's lymphomas.
Prevention or delay of onset of Brachyury-expressing cancers in individuals with pre-cancerous lesions or genetic predisposition.
Treatment to prevent or overcome chemotherapy resistance or radiation resistance in metastatic cancer patients.
Use as a prophylactic or therapeutic immunotherapy for metastatic cancer and associated conditions.
Treatment of diseases associated with Epstein Barr Virus infection using yeast-Brachyury immunotherapeutic compositions.
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