Engineered cells secreting therapeutic enzymes
Provided herein are mammalian cells comprising a first exogenous nucleic acid encoding a DNAse protein and a second exogenous nucleic acid encoding another DNAse protein, such as DNASE1 protein and DNASE1L3 protein, that have improved properties, including the ability to degrades extracellular chromatin and remove Neutrophil Extracellular Traps (NETs). Use of these cells, including the use in the treatment of a subject in need thereof, is also contemplated.
1 . An isolated mammalian cell modified to express:
at least one DNAse enzyme; and
at least one anti-B-cell maturation antigen (BCMA) antibody.
2 . The cell of claim 1 , wherein the cell is a mesenchymal stem cell.
3 . The cell of claim 1 , wherein the cell is a T cell.
4 . The cell of claim 3 , wherein the cell is a cluster of differentiation 8 (CD8+) cell.
5 . The cell of claim 1 , wherein the anti-BCMA antibody is a monoclonal antibody that binds BCMA.
6 . The cell of claim 1 , wherein the at least one DNAse enzyme and the at least one anti-BCMA antibody are expressed from one or more mRNAs.
7 . The cell of claim 6 , wherein the mRNA was introduced into the cell by electroporation.
8 . The cell of claim 1 , wherein the cell is a human cell.
9 . The cell of claim 1 , wherein the cell is a cluster of differentiation 4 (CD4+) cell.
10 . The cell of claim 1 , wherein the anti-BCMA antibody is a monoclonal, bispecific, dual-specific, or multi-specific antibody that binds BCMA.
11 . The cell of claim 1 , wherein the anti-BCMA antibody is a bispecific T-cell engager.
12 . The cell of claim 1 , wherein the at least one DNAse enzyme comprises DNASE1 and/or DNASE1L3.
13 . The cell of claim 1 , wherein the at least one DNAse enzyme comprises the amino acid sequence of any one of SEQ ID NOs: 1-3.
14 . The cell of claim 1 , wherein the anti-BCMA antibody is a bispecific antibody that comprises the amino acid sequence of SEQ ID NO: 22.
15 . A cell therapy product composition comprising a plurality of cells comprising the cell of claim 1 .