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-11938175-B2
Publication Date
2024-03-26
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 use a yeast vehicle and a cancer antigen containing at least one Brachyury antigen, and the immunotherapy can reduce, arrest, reverse, delay, or prevent metastatic progression of cancer. The compositions can be used prophylactically or therapeutically in individuals with cancers at various stages, including those with stage I-IV cancers, those at high risk, and those undergoing cancer therapies such as chemotherapy or radiation.
Brachyury is a mesodermal transcription factor implicated in early development and metastatic progression of cancer by promoting epithelial-mesenchymal transition (EMT) in tumor cells. It is expressed in a wide variety of human tumors and cancers, including metastatic and late-stage cancers across multiple tissue types. However, effective immunotherapeutic compositions targeting Brachyury remain needed.
The invention provides yeast-Brachyury immunotherapy that elicits Brachyury-specific immune responses, including CD4+ and CD8+ T cell responses, without exogenous adjuvants. These yeast-based compositions activate antigen-presenting cells and induce potent cytotoxic T lymphocyte responses effective against Brachyury-expressing tumors. This immunotherapy is adaptable for combination with other cancer antigens or therapies and is useful for personalized cancer treatment and prevention of metastatic progression.
Claims Coverage
The patent contains one independent claim defining an immunotherapeutic composition and two additional independent claims defining a recombinant nucleic acid molecule and a fusion protein, respectively. The claims disclose the core inventive features of the yeast-based immunotherapeutic composition expressing a specific Brachyury antigen.
Immunotherapeutic composition comprising whole, inactivated yeast and Brachyury antigen
The composition comprises (a) a whole, inactivated yeast or yeast lysate; (b) a cancer antigen comprising a Brachyury antigen with the amino acid sequence of positions 2-435 of SEQ ID NO:6; and (c) a pharmaceutically acceptable excipient suitable for human administration. The yeast may be heat inactivated, and from various genera including Saccharomyces cerevisiae.
Recombinant nucleic acid molecule encoding a fusion protein with a defined Brachyury antigen
A recombinant nucleic acid molecule encodes a fusion protein comprising at least one Brachyury antigen, wherein the Brachyury antigen comprises the amino acid sequence of positions 2-435 of SEQ ID NO:6.
Fusion protein comprising a defined Brachyury antigen
A fusion protein comprising at least one Brachyury antigen, wherein the Brachyury antigen comprises the amino acid sequence of positions 2-435 of SEQ ID NO:6.
The claims cover an immunotherapeutic composition that employs a whole, inactivated yeast vehicle expressing a Brachyury antigen of defined length and sequence, as well as the recombinant nucleic acid and fusion protein encoding this antigen, thus protecting compositions and constructs comprising the specified Brachyury antigen sequence in a yeast-based immunotherapy.
Stated Advantages
Controls or inhibits metastatic progression of cancer by targeting Brachyury-expressing tumor cells, including late-stage and metastatic cancers.
Elicits both potent CD4+ and CD8+ T cell-mediated immune responses against Brachyury without requiring exogenous adjuvants or immunostimulatory agents.
Can reduce or prevent chemotherapy-resistance and radiation-resistance of tumor cells.
Adaptable for combination with other tumor antigens and therapies, enabling personalized immunotherapy for cancer patients.
Can be administered repeatedly without loss of efficacy, offering sustained immunotherapeutic benefit.
Documented Applications
Prevention and/or treatment of cancers characterized by expression or overexpression of Brachyury, including metastatic cancers of the breast, small intestine, stomach, kidney, bladder, uterus, ovary, testes, lung, colon, pancreas, prostate, and lymphoid-origin tumors such as CLL and lymphomas.
Prevention or delay of onset of Brachyury-expressing cancers in individuals at high risk or with precancerous lesions.
Use in combination with chemotherapy and/or radiation therapy to reduce or prevent drug resistance in cancers.
Treatment or prevention of diseases associated with Epstein Barr Virus infection.
Generation and expansion of Brachyury-specific T cell responses in cancer patients and healthy individuals for immunotherapy.
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