Cancer vaccines and methods of producing and using same
Inventors
Lubaroff, David M. • Harris, Delbert L.
Assignees
University of Iowa Research Foundation UIRF • US Department of Veterans Affairs
Publication Number
US-11730799-B2
Publication Date
2023-08-22
Expiration Date
2039-10-18
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Abstract
A method of vaccinating a subject is provided, where a cancer protective response is produced. A first vaccine comprises an adenovirus vector comprising at least one nucleic acid molecule that produces a cancer protective response is administered, followed by one or more second vaccines comprising an alphavirus replicon particle comprising RNA comprising or produced from the nucleic acid molecule. In an embodiment the cancer is prostate cancer.
Core Innovation
Cancer vaccine protocols have faced challenges that limited their efficacy, particularly in achieving significant inhibition or elimination of cancer growth. Prostate cancer, being the most common non-skin cancer in males and a leading cause of cancer deaths, exemplifies these challenges. Standard therapies such as surgery or radiation are often not curative, with cancer recurrence prevalent and subsequent treatments only modestly extending survival with significant adverse effects and costs approaching $100,000 per patient.
The invention provides cancer vaccines that induce a cancer protective response by administering a first vaccine comprising a nucleic acid molecule delivered via an adenovirus vector, followed by one or more second vaccines comprising an alphavirus replicon particle containing RNA derived from the same nucleic acid molecule. This prime-boost vaccination approach, with the adenovirus vector administered first followed by the alphavirus vector replicon particle vaccine after about 14 days, synergistically enhances the cancer protective response, especially for prostate cancer.
The vaccines are replication deficient viral vectors that induce immune responses against cancer-specific antigens, exemplified by prostate specific antigen (PSA). The approach can reduce tumor growth, destroy tumors, or eliminate them completely. The vaccines can be monovalent or polyvalent, targeting multiple tumor-associated antigens. They can be produced safely and cost-effectively, with preclinical studies demonstrating tumor eradication using this prime-boost strategy, and are applicable to a wide spectrum of cancers where protective nucleic acid molecules are identified.
Claims Coverage
The patent contains three independent claims, each describing a method of producing an increased prostate cancer protective response or treating prostate cancer using a prime/boost vaccine regime involving adenovirus and alphavirus vectors.
Prime/boost vaccine regime with adenovirus and alphavirus vectors
Administering a first vaccine comprising a serotype 5 adenovirus (Ad5) vector comprising prostate specific antigen (PSA), followed after sufficient time for immune response to one or more second vaccines comprising an alphavirus replicon particle (VRP) comprising RNA from the same PSA antigen, where the alphavirus VRP is a TC-83 based vector.
Increased protective response with adenovirus prime and alphavirus boost
The protective response generated by administering the adenovirus prime followed by the alphavirus boost is increased compared to the reverse order where alphavirus VRP is the priming vaccine and Ad5 is the boosting vaccine.
Prostate cancer protective responses of reducing tumor growth or elimination
The methods include producing a protective response that comprises reducing growth of prostate tumors or elimination of prostate cancer tumors.
Administration parameters in the prime/boost regime
The second vaccine (alphavirus VRP) can be administered multiple times, for example three times, with at least about 14 days allowed after the initial adenovirus vaccination before boosting.
The claims cover a vaccination method specifically for prostate cancer using a prime/boost protocol where an Ad5 vector expressing PSA is administered first, followed by a TC-83 based alphavirus replicon particle vaccine also expressing PSA, resulting in an improved prostate cancer protective response over the reverse vaccination order. The method includes reduction and elimination of tumors with a defined administration timing and multiple dosing options.
Stated Advantages
The vaccines are safe, highly effective, and can be prepared quickly in 4 to 6 weeks at a cost considerably less than existing prostate cancer treatments.
The prime-boost vaccination strategy with adenovirus followed by alphavirus replicon particle produces a synergistic enhancement in cancer protection.
The protective response can lead to tumor eradication, tumor growth reduction, or complete elimination of tumors in patients.
The vaccines can be monovalent or polyvalent, allowing targeting of multiple tumor antigens.
Documented Applications
Treatment of prostate cancer in subjects having cancer, particularly for patients with recurrent disease after primary therapies such as surgery or radiation.
Vaccination for a wide range of cancers where tumor-associated antigen nucleic acid molecules can be identified, including both solid tumors and hematologic malignancies.
Combination therapies involving vaccination with anti-PD1 or anti-PD-L1 checkpoint inhibition antibodies to enhance anti-tumor immunity.
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