Yeast-based immunotherapy for Chordoma
Inventors
Rodell, Timothy C. • Apelian, David • Palena, Claudia • Schlom, Jeffrey
Assignees
GlobeImmune Inc • US Department of Health and Human Services
Publication Number
US-10507235-B2
Publication Date
2019-12-17
Expiration Date
2034-03-19
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Abstract
One embodiment of the invention relates to a method to treat chordoma in an individual who has chordoma. The method includes the step of administering to an individual who has chordoma, an immunotherapeutic composition comprising: (a) a yeast vehicle; and (b) a cancer antigen comprising at least one Brachyury antigen. Another embodiment of the invention relates to the use of an immunotherapeutic composition comprising a yeast vehicle and a cancer antigen comprising at least one Brachyury antigen to chordoma in an individual who has chordoma. Yet another embodiment of the invention relates to the use an immunotherapeutic composition comprising a yeast vehicle.
Core Innovation
The invention relates to yeast-based immunotherapeutic compositions and methods for the prevention and/or treatment of chordoma. Specifically, it involves administering an immunotherapeutic composition comprising a yeast vehicle and a cancer antigen comprising at least one Brachyury antigen to an individual who has chordoma. The invention also covers the use of such compositions to prevent or delay the onset of chordoma, including in individuals with a history of familial chordoma.
Chordoma is a rare bone cancer that arises from embryonic remnants of the notochord and has a poor prognosis, being aggressive and locally invasive. It commonly occurs in the sacrum, skull base, and mobile spine. Despite treatments like aggressive surgical resection and radiation therapy, many chordomas recur or progress. Conventional chemotherapy is generally ineffective, and targeted therapies such as tyrosine kinase inhibitors offer limited benefit. Thus, there is a need for improved therapeutic approaches for chordoma, including options for prevention or delaying onset in familial chordoma cases.
Claims Coverage
The patent includes one independent claim detailing a method of treating chordoma using a specific immunotherapeutic composition. There are multiple inventive features related to the components of the composition, target patient populations, treatment regimens, and combination with other therapies.
Treatment of chordoma using a yeast-based immunotherapeutic composition
A method for treating chordoma by administering to an individual an immunotherapeutic composition comprising a yeast vehicle and a cancer antigen comprising at least one Brachyury antigen with an amino acid sequence represented by positions 2-435 of SEQ ID NO:6.
Treatment targeting specific chordoma presentations
The method applies to individuals having non-resectable, locally recurring lesions, oligometastatic disease, first recurrence of non-resectable or resectable lesions, or metastatic disease.
Combination with other cancer therapies
The immunotherapeutic composition can be administered to individuals being treated or previously treated with other cancer therapies such as radiation therapy (concurrent or sequential), tumor resection, chemotherapy, and targeted drug therapies including tyrosine kinase inhibitors, EGFR inhibitors, and STAT3 inhibitors.
Variants and forms of the Brachyury antigen
The Brachyury antigen used in the composition can include sequences of SEQ ID NO:18, SEQ ID NO:2 or fusion proteins SEQ ID NO:8 or SEQ ID NO:20, or amino acid sequences at least 95% identical thereto.
Yeast vehicle specifications
The yeast vehicle is a whole inactivated yeast, preferably heat-inactivated, and expresses the antigen. The yeast is from Saccharomyces cerevisiae species.
Formulation and administration protocols
The composition is formulated in pharmaceutically acceptable excipients suitable for injection, with dosing ranging from about 0.1 Y.U. to about 100 Y.U. The immunotherapeutic composition can be administered weekly, every other week, monthly, or specific regimens such as weekly for 5 weeks followed by monthly or at two-week intervals for 7 rounds followed by monthly. Multiple administration sites can be used to form a single dose.
Concurrent administration with other therapies
The immunotherapeutic composition may be administered concurrently with other cancer therapies, including radiation therapy.
The claims cover a method to treat chordoma by administering a yeast vehicle-based immunotherapeutic composition incorporating Brachyury antigen sequences. The invention specifies targeted patient groups, combination with other therapies, various forms of Brachyury antigen, yeast vehicle types, and administration protocols.
Stated Advantages
The immunotherapeutic composition is expected to be safe and well tolerated with no significant toxicities.
The composition produces treatment-emergent Brachyury-specific T cell responses in treated subjects.
Treatment may stabilize disease, extend recurrence free survival or overall survival, and reduce tumor growth rate.
It can improve progression free survival and response rates as measured by RECIST or Choi criteria.
Documented Applications
Treatment of chordoma in individuals with non-resectable, locally recurring lesions, oligometastatic disease, first recurrence of lesions, metastatic disease.
Prevention or delay of onset of chordoma in individuals with familial chordoma or predisposition to chordoma.
Use as monotherapy or in combination with other therapies such as surgical resection, radiation therapy, chemotherapy, targeted drug therapies, and additional immunotherapeutics.
Clinical trials for chordoma patients including phase 1 and phase 2 trials evaluating safety, immunogenicity, progression-free survival, tumor response rates, and disease stabilization.
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