The present invention relates to a cell which co-expresses: (i) a first chimeric antigen receptor (CAR) at the cell surface, comprising an antigen-binding domain which binds to CD19; (ii) a second CAR at the cell surface, comprising an antigen-binding domain which binds to CD22; (iii) dominant negative SHP2 (dSHP2); and (iv) dominant negative TGF receptor II (dnTGFRII).

A chimeric antigen receptor (CAR), including an antigen-binding domain, a CD8 or CD28 hinge domain, a DAP10 cytoplasmic domain, a 2B4 cytoplasmic domain, and a CD3z cytoplasmic domain, where the CAR is expressed in natural killer (NK) cells. A method for treating cancer, including administering a therapeutically effective amount of a composition containing a NK cell that expresses the CAR, or a therapeutically effective amount of a cellular therapeutic agent containing a NK cell that expresses the CAR, to a subject in need thereof.

Provided herein are humanized mouse models and methods for determining whether administration of engineered immune cell therapies likely elicit cytokine release syndrome and/or determining the efficacy of an anti-disease therapy. Further, the models provided herein may be used to test the efficacy of different anti-CRS therapies.

The present invention provides a chimeric antigen receptor (CAR) which binds a target antigen having a bulky extra-cellular domain, wherein the CAR comprises a Fab antigen binding domain. The present invention also provides nucleic acid sequences and constructs encoding such a CAR, cells expressing such a CAR and their therapeutic uses.

The present invention relates to an engineered immune cell endowed with a new CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect said immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.

The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) that help the immune cells to direct their immune response against infected or malignant cells. These exogenous coding sequences are more particularly inserted under the transcriptional control of endogenous gene promoters that are sensitive to immune cells activation. Such method allows the production of safer immune primary cells of higher therapeutic potential.

An aptamer-based switch technology is provided that enhances control of the use of chimeric antigen receptor (CAR)-related immunotherapies. The aptamer-based switch utilizes a synthetic bridge molecule containing a target-binding aptamer bound through a linker to a CAR-binding aptamer. A system containing a CAR and a corresponding aptameric bridge provides an immunotherapy platform that: (i) can be targeted to any desired antigen by choosing the target-binding aptamer of the bridge. (ii) can be redirected from one target to another by changing the target-binding aptamer: (iii) can be dosed according to the changing needs of an individual patient overtime by altering the administration protocol for the bridge: (iv) can be switched on or off quickly or gradually: (v) can be used as a companion diagnostic for a specific CAR therapy: (vi) can be integrated with either in vivo or ex vivo CAR expression: (vii) is non-immunogenic; and (viii) has low production costs.

An embodiment of the invention provides chimeric antigen receptor (CAR) amino acid constructs. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CAR constructs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed. Methods of making the CAR constructs are disclosed.

The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising an antigen-binding domain, wherein the antigen-binding domain of the first CAR binds to CD19 and the antigen-binding domain of the second CAR binds to CD22.

The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising an antigen-binding domain, wherein the antigen-binding domain of the first CAR binds to CD19 and the antigen-binding domain of the second CAR binds to CD22.