Combinatorial cancer immunotherapy
AssigneeSenti Biosciences, Inc.
InventorsTimothy Kuan-Ta Lu, Russell Morrison Gordley, Jack Tzu-Chiao Lin, Brian Scott Garrison, Philip Janmin Lee, Alba Gonzalez-Junca, Don-Hong Wang
Life of this patent
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Abstract
Provided herein are methods and compositions for dynamically controlling and targeting multiple immunosuppressive mechanisms in cancer. Some aspects provide cells engineered to produce multiple effector molecules, each of which modulates a different immunosuppressive mechanisms of a tumor, as well as methods of using the cells to treat cancer, such as ovarian, breast, or colon cancer.
Claims18
A method of reducing tumor volume in a subject, the method comprising delivering to a subject having a tumor a composition comprising mesenchymal stem cells engineered to produce multiple effector molecules comprising at least a first effector molecule and a second effector molecule that each modulate tumor-mediated immunosuppressive mechanisms in an effective amount to reduce the volume of the tumor, wherein the first effector molecule comprises interleukin 12 (IL-12),
- wherein the multiple effector molecules except the first effector molecule are each independently selected from the group consisting of:
- cytokines, receptors/ligands, antibodies, nucleotides, peptides, and enzymes,
- wherein the composition comprises (a) a first mesenchymal stem cell engineered to produce the first effector molecule and (b) a second mesenchymal stem cell engineered to produce the second effector molecule, and
- wherein tumor reduction is greater than tumor reduction following administration of either the first mesenchymal stem cell alone or the second mesenchymal stem cell alone.
A method of modulating an immunosuppressive mechanism in a subject, the method comprising delivering to a subject a composition comprising mesenchymal stem cells engineered to produce multiple effector molecules comprising at least a first effector molecule and a second effector molecule that each modulate tumor-mediated immunosuppressive mechanisms in an effective amount to modulate the immunosuppressive mechanism, wherein the first effector molecule comprises IL-12,
- wherein modulating the immunosuppressive mechanism comprises increasing an immune response in the subject,
- wherein the multiple effector molecules except the first effector molecule are each independently selected from the group consisting of:
- cytokines, receptors/ligands, antibodies, nucleotides, peptides, and enzymes,
- wherein the composition comprises (a) a first mesenchymal stem cell engineered to produce the first effector molecule and (b) a second mesenchymal stem cell engineered to produce the second effector molecule, and
- wherein the increased immune response is greater than the immune response following administration of either the first mesenchymal stem cell alone or the second mesenchymal stem cell alone.
Dependencies are inferred from the claim text.