Compositions and methods for tumor transduction
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Publication Number
US-10066023-B2
Publication Date
2018-09-04
Expiration Date
Abstract
The invention relates to cancer therapeutics, in particular, the system of making cancer cells more susceptible to effector cells by introduction of cellular therapy targets into the cancer cells.
Core Innovation
The invention describes tumor transduction using an adeno-associated viral (AAV) vector, including a chimeric AAV/phage (AAVP) vector, to deliver a nucleotide sequence encoding a secreted fusion protein. The secreted fusion protein comprises an antibody or antigen-binding fragment that binds a tumor antigen and creates a tumor cell coating or modification intended to present a cell therapy target to effector cells.
The secreted fusion protein further comprises a polypeptide antigen that is not a target for endogenous immune cells in an individual, while the polypeptide antigen is a target antigen for an administered therapeutic selected from cellular therapeutics, antibodies, or antibody-drug conjugates. In described embodiments, the administered therapeutic includes cellular therapeutics such as CAR-T, TCR-T, or NK, and tumor killing is induced through binding to the fusion protein.
Fusion proteins are described as modular and configurable, combining an antibody or antigen-binding fragment component with therapeutic target/scaffold components, and optionally additional therapeutic payloads. The document lists many candidate tumor antigens for antibody binding and provides example constructs, and experimental results are reported showing that AAV-transduced cells express functional fusion proteins and induce IFNb3 and CAR19 T-cell cytotoxicity.
Claims Coverage
The independent claims cover an AAV or chimeric AAV/phage vector encoding a secreted fusion protein with defined antibody-binding and polypeptide-antigen targeting relationships, and a method of treating a tumor-bearing subject by administering that vector followed by tumor killing induced by binding between the fusion protein and an administered therapeutic. Each independent claim centers on the vector type and secreted fusion protein composition, and on the therapeutic binding-to-killing relationship in the treating method.
Secreted fusion protein for tumor antigen targeting and administered therapeutic targeting
An adeno-associated viral (AAV) vector, or a chimeric AAV/phage (AAVP) vector, comprising a nucleotide sequence encoding a secreted fusion protein comprising an antibody or antigen-binding fragment thereof that binds a tumor antigen and a polypeptide antigen that is not a target for endogenous immune cells in an individual and is a target antigen for an administered therapeutic selected from cellular therapeutics, antibodies, or antibody-drug conjugates.
Treating a tumor-bearing subject via administered vector and binding-induced tumor killing
A method of treating a subject having a tumor, comprising administering an adeno-associated viral (AAV) vector, or a chimeric AAV/phage (AAVP), vector comprising a nucleotide sequence encoding a fusion protein comprising an antibody or antigen-binding fragment thereof that binds a tumor antigen and a polypeptide antigen that is not a target antigen for endogenous immune cells in an individual and is a target antigen for an administered therapeutic selected from cellular therapeutics, antibodies, or antibody-drug conjugates, wherein the cellular therapeutic, antibody, or antibody-drug conjugate binds to the fusion protein and said binding induces killing of the tumor, thereby treating the subject.
Overall, the claim set is directed to AAV/AAVP-delivered secreted fusion proteins that bind tumor antigens and present a polypeptide antigen as a target for an administered therapeutic, with treatment defined by binding to the fusion protein that induces tumor killing.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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