Back to results
US 2021/0228640 A1Published application
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, Daniel Frimannsson
Life of this patent
Estimating the term…
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.
Claims20
A method of treating a subject having cancer, wherein the method comprises delivering to a subject an engineered cell in an effective amount to induce an immune response, wherein the engineered cell comprises:
- a) a promoter;
- and
- b) an exogenous polynucleotide sequence comprising an expression cassette described in a formula, oriented from 5′ to 3′, comprising
- S1-E1-L-S2-E2
- wherein
- S1 comprises a polynucleotide sequence encoding a first signal peptide,
- E1 comprises a polynucleotide sequence encoding a first effector molecule,
- L comprises a linker polynucleotide sequence,
- S2 comprises a polynucleotide sequence encoding a second signal peptide,
- E2 comprises a polynucleotide sequence encoding a second effector molecule, and
- wherein the promoter is operably linked to the expression cassette, the first signal peptide is operably linked to the first effector molecule, and the second signal peptide is operably linked to the second effector molecule,
- wherein the engineered cell is selected from the group consisting of:
- a mesenchymal stem cell (MSC), stem cell, immune cell, natural killer (NK) cell, NKT cell, innate lymphoid cell, mast cell, eosinophil, basophil, monocyte, macrophage, neutrophil, myeloid cell, dendritic cell, and B cell, and
- wherein
- (a) the first effector molecule comprises an IL12p70 fusion protein and the second effector molecule comprises CCL21a, IL7, IL15, IL21, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein,
- (b) the first effector molecule comprises CCL21a, IL7, IL15, IL21, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein and the second effector molecule comprises an IL12p70 fusion protein,
- (c) the first effector molecule comprises IL21 and the second effector molecule comprises CCL21a, IL7, IL15, IL18, an IL12p70 fusion protein, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein, or
- (d) the first effector molecule comprises CCL21a, IL7, IL15, IL18, an IL12p70 fusion protein, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein and the second effector molecule comprises IL21.
15 more elements
An engineered cell comprising:
- a) a promoter;
- and
- b) an exogenous polynucleotide sequence comprising an expression cassette described in a formula, oriented from 5′ to 3′, comprising
- S1-E1-L-S2-E2
- wherein
- S1 comprises a polynucleotide sequence encoding a first signal peptide,
- E1 comprises a polynucleotide sequence encoding a first effector molecule,
- L comprises a linker polynucleotide sequence,
- S2 comprises a polynucleotide sequence encoding a second signal peptide,
- E2 comprises a polynucleotide sequence encoding a second effector molecule, and
- wherein the promoter is operably linked to the expression cassette, the first signal peptide is operably linked to the first effector molecule, and the second signal peptide is operably linked to the second effector molecule, and
- wherein the engineered cell is selected from the group consisting of:
- a mesenchymal stem cell (MSC), stem cell, immune cell, natural killer (NK) cell, NKT cell, innate lymphoid cell, mast cell, eosinophil, basophil, monocyte, macrophage, neutrophil, myeloid cell, dendritic cell, and B cell, and
- wherein
- (a) the first effector molecule comprises an IL12p70 fusion protein and the second effector molecule comprises CCL21a, IL7, IL15, IL21, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein,
- (b) the first effector molecule comprises CCL21a, IL7, IL15, IL21, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein and the second effector molecule comprises an IL12p70 fusion protein,
- (c) the first effector molecule comprises IL21 and the second effector molecule comprises CCL21a, IL7, IL15, IL18, an IL12p70 fusion protein, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein, or
- (d) the first effector molecule comprises CCL21a, IL7, IL15, IL18, an IL12p70 fusion protein, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein and the second effector molecule comprises IL21.
15 more elements
An exogenous polynucleotide sequence comprising a promoter and an expression cassette described in a formula, oriented from 5′ to 3′, comprising
- S1-E1-L-S2-E2
- wherein
- S1 comprises a polynucleotide sequence encoding a first signal peptide,
- E1 comprises a polynucleotide sequence encoding a first effector molecule,
- L comprises a linker polynucleotide sequence,
- S2 comprises a polynucleotide sequence encoding a second signal peptide,
- E2 comprises a polynucleotide sequence encoding a second effector molecule, and
- wherein the promoter is operably linked to the expression cassette, the first signal peptide is operably linked to the first effector molecule, and the second signal peptide is operably linked to the second effector molecule, and
- wherein
- (a) the first effector molecule comprises an IL12p70 fusion protein and the second effector molecule comprises CCL21a, IL7, IL15, IL21, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein,
- (b) the first effector molecule comprises CCL21a, IL7, IL15, IL21, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein and the second effector molecule comprises an IL12p70 fusion protein,
- (c) the first effector molecule comprises IL21 and the second effector molecule comprises CCL21a, IL7, IL15, IL18, an IL12p70 fusion protein, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein, or
- (d) the first effector molecule comprises CCL21a, IL7, IL15, IL18, an IL12p70 fusion protein, Flt3L, an anti-PD1 antibody, CD40L, or a CXCL10-CXCL11 fusion protein and the second effector molecule comprises IL21.
10 more elements
Dependencies are inferred from the claim text.