Compositions and methods for tumor transduction
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11059904-B2
Publication Date
2021-07-13
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 adeno-associated viral (AAV) vector, oncolytic viral vector, or chimeric AAV/phage (AAVP) vector comprising a nucleotide sequence encoding one or more secreted fusion proteins. Each secreted fusion protein comprises a bispecific antibody that binds two tumor antigens, or an antigen-binding fragment of the bispecific antibody, together with a polypeptide antigen. The polypeptide antigen is not a target for endogenous immune cells in an individual, but is a target antigen for an administered therapeutic selected from cellular therapeutics, antibodies, and antibody-drug conjugates.
In some configurations, the two tumor antigens are selected from an enumerated set of tumor antigens. The antigen-binding portion can be defined using bispecific formats or antigen-binding fragments such as Fab, scFv, Fv, and/or VHH, including configurations using two scFvs. The polypeptide antigen can be restricted to B cell antigens, including CD19 or CD22, and the tumor-antigen scope can be further limited by the selected antigen list.
The invention also covers treating a subject having a tumor by administering the above AAV, oncolytic viral, or AAVP vector encoding secreted fusion proteins. The disclosed treatment includes a cellular therapeutic, antibody, or antibody-drug conjugate that binds to the fusion protein, such that the binding induces killing of the tumor. Further, the invention includes configurations where the vector transduces or transforms tumor cells in the subject to produce the secreted fusion proteins.
Additionally, the invention covers vectors encoding two or more different secreted fusion proteins, where each fusion protein comprises antibody(s) or antigen-binding fragments that bind one or more tumor antigen and includes a polypeptide antigen that is not a target for endogenous immune cells. The administered therapeutic is again selected from cellular therapeutics, antibodies, and antibody-drug conjugates, enabling tumor killing in the context of binding between the administered therapeutic and the secreted fusion proteins.
Claims Coverage
The provided independent claims are clm-00001, clm-00010, and clm-00023, collectively specifying three core inventive structures and their use. Across these claims, the inventive subject matter centers on secreted fusion proteins encoded by AAV, oncolytic viral, or chimeric AAV/phage (AAVP) vectors, with defined antigen-binding components and a polypeptide antigen targeted by administered therapeutics; the treatment claim further requires induced tumor killing through binding by the administered therapeutic.
Secreted bispecific fusion proteins encoded by AAV, oncolytic, or AAVP vector
An adeno-associated viral (AAV) vector, an oncolytic viral vector, or a chimeric AAV/phage (AAVP) vector comprising a nucleotide sequence encoding one or more secreted fusion proteins, each fusion protein comprising: a bispecific antibody that binds two tumor antigens, or antigen-binding fragments of the bispecific antibody; and a polypeptide antigen wherein the polypeptide antigen 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, and antibody-drug conjugates.
Treating tumor by administering secreted bispecific fusion protein vector with therapeutic that binds the fusion protein
A method of treating a subject having a tumor, comprising administering to the subject: an AAV vector, an oncolytic viral vector, or a chimeric AAV/phage (AAVP) vector comprising a nucleotide sequence encoding one or more secreted fusion proteins, each fusion comprising a bispecific antibody that binds two tumor antigens, or antigen-binding fragments of the bispecific antibody, 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, and antibody-drug conjugates; and the cellular therapeutic, antibody, or antibody-drug conjugate, 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.
Secreted multi-fusion protein vector with tumor-antigen antibody fragments and non-endogenous-target polypeptide antigen
An adeno-associated viral (AAV) vector, an oncolytic viral vector, or a chimeric AAV/phage (AAVP) vector comprising a nucleotide sequence encoding two or more different secreted fusion proteins, each fusion protein comprising: one or more antibodies, or antigen-binding fragments thereof, that bind one or more tumor antigen; and a polypeptide antigen wherein the polypeptide antigen 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, and antibody-drug conjugates.
Across clm-00001, clm-00010, and clm-00023, claim coverage is focused on vectors that encode secreted fusion proteins with defined tumor-antigen binding and a polypeptide antigen that is not an endogenous immune-cell target but is a target for administered therapeutics, with tumor killing being induced by binding of the administered therapeutic to the fusion protein in the method claim.
Stated Advantages
Documented Applications
No documented applications found
Interested in licensing this patent?