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US 11,655,455 B2Granted
Enhanced systems for cell-mediated oncolytic viral therapy
AssigneeCalidi Biotherapeutics, Inc.
InventorsAntonio Fernandez Santidrian, Duong Hoang Nguyen, Dobrin Draganov
Life of this patent
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Abstract
Provided herein are enhanced systems for potentiating cell-mediated oncolytic viral therapy. Also provided are modified viruses for such systems, and methods of treatment of cancers by administering such systems.
Claims63
A cell-assisted viral expression system (CAVES), comprising a carrier cell and an oncolytic virus, wherein:
- the carrier cell comprising the oncolytic virus was produced by infection of the cell with virus at an MOI of 0.001 to <1.0, followed by incubation for 6 or more hours up to less than 96 hours under conditions in which proteins encoded by the virus are expressed, whereby the carrier cell expresses at least one immunomodulatory protein or recombinant therapeutic protein encoded by the virus by virtue of association of the virus with the carrier cell;
- and
- the carrier cell is not a tumor cell.
A method of producing a cell-assisted viral expression system (CAVES), comprising:
- incubating carrier cells and an oncolytic virus for infection of the cell with virus at an MOI of 0.001 to <1.0, for 6 or more hours up to less than 48 hours under conditions in which the virus expresses encoded proteins, whereby carrier cells express at least one immunomodulatory protein or recombinant therapeutic protein encoded by the virus by virtue of association of the virus with the carrier cells to produce a cell-assisted viral expression system (CAVES);
- recovering the cell-assisted viral expression system cells;
- and
- storing them at reduced temperature in cryopreservation medium to produce stored cell-assisted viral expression systems (CAVES).
1 more element
A pharmaceutical composition, comprising in a pharmaceutically acceptable vehicle, a cell-assisted viral expression system (CAVES), wherein:
- the CAVES comprises a carrier cell and an oncolytic virus;
- the carrier cell comprising the oncolytic virus was produced by infection of the cell with virus at an MOI of 0.001 to <1.0, followed by incubation for 6 or more hours up to less than 96 hours under conditions in which proteins encoded by the virus are expressed, whereby the carrier cell expresses at least one immunomodulatory protein or recombinant therapeutic protein encoded by the virus by virtue of association of the virus with the carrier cell.
A cell-assisted viral expression system (CAVES), comprising a carrier cell and an oncolytic virus, wherein:
- the carrier cell comprising the oncolytic virus was produced by infection of the cell with virus at an MOI of 0.001 to <1.0, followed by incubation for 6 or more hours up to less than 96 hours under conditions in which proteins encoded by the virus are expressed, whereby the carrier cell expresses at least one immunomodulatory protein or recombinant therapeutic protein encoded by the virus by virtue of association of the virus with the carrier cell;
- and
- the oncolytic virus is selected from among an adenovirus, herpes simplex virus, Newcastle disease virus, avesicular stomatitis virus, measles virus, reovirus, cytomegalovirus (CMV), lentivirus, parvovirus, picornavirus, rhabdovirus, alphavirus, Maraba virus, and retrovirus.
A cell-assisted viral expression system (CAVES), comprising a carrier cell and an oncolytic virus, wherein:
- the carrier cell comprising the oncolytic virus was produced by infection of the cell with virus at an MOI of 0.001 to <1.0, followed by incubation for 6 or more hours up to less than 96 hours under conditions in which proteins encoded by the virus are expressed, whereby the carrier cell expresses at least one immunomodulatory protein or recombinant therapeutic protein encoded by the virus by virtue of association of the virus with the carrier cell;
- the carrier cell has been treated or modified or both to enhance the immunosuppressive properties and/or immunoprivileged properties of the cell for administration to a human subject;
- the virus is a vaccinia virus that contains a mutation in the A34R protein for enhanced extracellular enveloped virus (EEV) production;
- and
- optionally, the cell has been treated or modified to enhance amplification of the virus in the cell.
2 more elements
A cell-assisted viral expression system (CAVES), comprising a carrier cell and an oncolytic virus, wherein:
- the carrier cell comprising the oncolytic virus was produced by infection of the cell with virus at an MOI of 0.001 to <1.0, followed by incubation for 6 or more hours up to less than 96 hours under conditions in which proteins encoded by the virus are expressed, whereby the carrier cell expresses at least one immunomodulatory protein or recombinant therapeutic protein encoded by the virus by virtue of association of the virus with the carrier cell;
- the carrier cell has been treated or modified or both to enhance the immunosuppressive properties and/or immunoprivileged properties of the cell for administration to a human subject;
- and
- the virus is a vaccinia virus that is thymidine kinase (TK)+.
1 more element
A cell-assisted viral expression system (CAVES), comprising a carrier cell and an oncolytic virus, wherein:
- the carrier cell comprising the oncolytic virus was produced by infection of the cell with virus at an MOI of 0.001 to <1.0, followed by incubation for 6 or more hours up to less than 96 hours under conditions in which proteins encoded by the virus are expressed, whereby the carrier cell expresses at least one immunomodulatory protein or recombinant therapeutic protein encoded by the virus by virtue of association of the virus with the carrier cell;
- the carrier cell has been treated or modified or both to enhance the immunosuppressive properties and/or immunoprivileged properties of the cell for administration to a human subject;
- and
- the virus is a vaccinia virus that is an ACAM1000 virus, an ACAM2000 virus, or a virus propagated from an ACAM1000 or ACAM2000 virus.
1 more element
Dependencies are inferred from the claim text.