Cells for immunotherapy engineered for targeting antigen present both on immune cells and pathological cells
Inventors
Duchateau, Philippe • Poirot, Laurent
Assignees
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Publication Number
US-11692169-B2
Publication Date
2023-07-04
Expiration Date
Abstract
Methods of developing genetically engineered immune cells for immunotherapy, which can be endowed with Chimeric Antigen Receptors targeting an antigen marker that is common to both the pathological cells and said immune cells (ex: CD38, CS1 or CD70) by the fact that the genes encoding said markers are inactivated in said immune cells by a rare cutting endonuclease such as TALEN, Cas9 or argonaute.
Core Innovation
The invention prepares an immune cell for immunotherapy by inactivating or mutating a gene encoding a CD38 antigen marker and expressing in the immune cell a transgene encoding a chimeric antigen receptor (CAR) directed against the CD38 antigen marker. The disclosure combines CD38 antigen marker gene inactivation or mutation with CD38-targeted CAR immunotherapy in the same immune cell population.
In the described embodiments, a rare-cutting endonuclease is used to inactivate or mutate the gene encoding the CD38 antigen marker, including TAL-nucleases, and expression can be achieved from transfected mRNA in the immune cells. The resulting engineered immune cell comprises the inactivated or mutated CD38 antigen marker gene and a CAR transgene directed against the CD38 antigen marker.
The immune cells encompassed by the claims include natural killer cells, and the resulting immune cells can be purified by excluding cells that present a CD38 antigen marker on their surface. The invention thus provides an engineered immune cell for immunotherapy with CD38 gene inactivation or mutation and CAR expression.
Claims Coverage
The independent claim set includes three independent claims, directed to preparation of an immune cell for immunotherapy with CD38 gene inactivation plus CAR expression, preparation of an immune cell by CD38 gene inactivation using a rare-cutting endonuclease, and an engineered immune cell containing an inactivated or mutated CD38 antigen marker gene cleaved by a rare-cutting endonuclease together with a CAR transgene. The inventive features are centered on coupling CD38 gene inactivation or mutation with CAR-directed immunotherapy and defining the CD38 gene editing mechanism as cleavage by a rare-cutting endonuclease.
CD38 gene inactivation or mutation with CAR expression
Inactivating or mutating a gene encoding a CD38 antigen marker in an immune cell, and expressing in said immune cell a transgene encoding a chimeric antigen receptor (CAR) directed against said CD38 antigen marker.
CD38 gene inactivation or mutation using a rare-cutting endonuclease
Inactivating or mutating a gene encoding a CD38 antigen marker in an immune cell using a rare-cutting endonuclease.
Engineered immune cell with rare-cutting endonuclease cleavage of CD38 gene and CAR transgene
An inactivated or mutated gene encoding a CD38 antigen marker, wherein said CD38 antigen marker is inactivated or mutated by cleavage with a rare-cutting endonuclease and a transgene encoding a chimeric antigen receptor (CAR).
Across the independent claims, the core claim coverage is the preparation of immune cells for immunotherapy in which a CD38 antigen marker gene is inactivated or mutated and a CAR transgene directed to the CD38 antigen marker is expressed, with the gene inactivation or mutation mechanism defined as cleavage with a rare-cutting endonuclease in the broader claim formulations. Dependent refinements shown in the provided claim set further specify purification by excluding cells presenting surface CD38, specify TAL-nuclease and transfected mRNA expression formats, and restrict the immune cell type to natural killer cells.
Stated Advantages
The immune cell is not susceptible in the CD38-targeted setting, while still expressing a CAR directed against CD38.
Documented Applications
Immunotherapy using CARs directed against CD38 antigen marker in an engineered immune cell prepared by inactivating or mutating the CD38 antigen marker gene.
Immunotherapy approaches that include engineered immune cells where the CD38 antigen marker gene is inactivated or mutated using a rare-cutting endonuclease and a CAR transgene is expressed.
Use in immunotherapy.
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