Compositions and methods for tumor transduction
Inventors
Assignees
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Publication Number
US-10072094-B2
Publication Date
2018-09-11
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 relates to cancer immunotherapy using viral vectors that encode fusion proteins combining an antibody, or an antigen-binding fragment thereof, that binds a tumor antigen with a polypeptide antigen component. The fusion protein is configured such that the polypeptide antigen is not a target antigen for endogenous immune cells in an individual, while the polypeptide antigen serves as a target antigen for an administered therapeutic selected from cellular therapeutics, antibodies, or antibody-drug conjugates.
A first aspect of the invention provides an adenoviral vector comprising a nucleotide sequence encoding the fusion protein with the antibody portion and the polypeptide antigen portion defined by the non-endogenous target antigen and the administered therapeutic target antigen relationship. A second aspect provides an oncolytic viral vector with the same fusion protein architecture, also defined by the tumor-antigen binding component and the polypeptide antigen that is not a target antigen for endogenous immune cells but is targeted by an administered therapeutic from the stated group.
A further aspect of the invention provides a method of treating a subject having a tumor by administering the oncolytic viral vector encoding the fusion protein. The document also describes embodiments in which the fusion proteins can be used to present or direct a cellular-therapy target on the tumor surface or within the tumor microenvironment, with examples including CD19 and CAR19-related concepts.
Claims Coverage
The document includes three independent claims: one adenoviral vector claim, one oncolytic viral vector claim, and one method claim. Across these independent claims, the inventive framework consistently couples a tumor-antigen binding antibody/antigen-binding fragment with a polypeptide antigen defined by being non-endogenous for immune cells yet targetable by an administered therapeutic selected from cellular therapeutics, antibodies, or antibody-drug conjugates.
Adenoviral vector encoding a tumor-antigen binding fusion protein with a non-endogenous immune target antigen
An adenoviral 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 wherein the polypeptide antigen 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.
Oncolytic viral vector encoding a tumor-antigen binding fusion protein with a non-endogenous immune target antigen
An oncolytic viral 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 wherein the polypeptide antigen 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.
Method of treating a tumor by administering an oncolytic viral vector with a tumor-antigen binding fusion protein
A method of treating a subject having a tumor, comprising administering to the subject an oncolytic viral 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 wherein the polypeptide antigen 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.
Claim coverage centers on fusion-protein payloads carried by viral vectors where the antibody/antigen-binding fragment binds a tumor antigen and the accompanying polypeptide antigen is defined relative to endogenous immune targeting and the ability of an administered therapeutic to target that polypeptide antigen. The method claim then applies the oncolytic viral vector administration to treating a subject with a tumor.
Stated Advantages
Documented Applications
Treating a subject having a tumor by administering an oncolytic viral vector that encodes a fusion protein with a tumor-antigen-binding antibody/antigen-binding fragment and a polypeptide antigen that is not a target antigen for endogenous immune cells but is targeted by an administered therapeutic selected from cellular therapeutics, antibodies, or antibody-drug conjugates.
Cancer immunotherapy use cases involving functional CD19-scFv fusion proteins from transduced cells, reporting induction of IFNγ and CAR19 T-cell cytotoxicity against target tumor cells [procedural detail omitted for safety].
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