US 12,760,100 B2 · Methods and compositions to improve the safety and efficacy of cellular therapies

Abstract

Described herein are novel compositions and methods to improve the safety and efficacy of adoptive cellular therapies of cancer, infection, allergic, degenerative and immune disorders. The disclosure provides a) novel methods and compositions to reduce the accidental insertion of chimeric receptors into cancer cells; b) novel methods to measure the titer of viral vectors; c) novel compositions to generate antigen masking receptors and methods to use such receptors to protect normal cells from immunotherapeutic agents; d) novel compositions and methods to extend the life-span of allogeneic cells, including allogeneic CAR-T cells; e) novel compositions and methods to ameliorate the side-effects of cellular therapies and f) novel compositions of Synthetic Immune Receptors and Ab-TCRs with mutant TCRα constant chains.

Claims26

Dependent claims

A method for reducing the insertion of a nucleic acid encoding an antigen binding receptor (ABR) into a cell expressing an antigen that is targeted by the ABR comprising contacting the cell with a viral vector comprising a nucleic acid encoding the ABR, wherein the ABR is present on an envelope of the viral vector, in the presence of an exogenous inhibitory agent, wherein the exogenous inhibitory agent interferes with the interaction of an antigen binding domain of the ABR and the antigen thereby reducing insertion of the nucleic acid encoding the ABR into the cell expressing the antigen.

A method for reducing the insertion of a nucleic acid encoding an antigen binding receptor (ABR) into a cell expressing an antigen that is targeted by the ABR, wherein a viral vector comprising the nucleic acid encoding the ABR is produced using packaging cells, the method comprising one or more of the following options:

(a) contacting the cell expressing the antigen with the viral vector comprising the nucleic acid encoding the ABR in the presence of an exogenous inhibitory agent, wherein the ABR is present on an envelope of the viral vector, and wherein the exogenous inhibitory agent interferes with the interaction between an antigen binding domain of the ABR and the antigen, wherein the cell expressing the antigen is contacted with the exogenous inhibitory agent before and/or during the step of contacting the cell expressing the antigen with the viral vector;
(b) reducing or eliminating expression of the ABR, wherein the ABR is expressed on a surface of the packaging cells that are used to produce the viral vector;
(c) co-expressing, in the packaging cells that are used to produce the viral vector, the antigen or a fragment thereof that is recognized by the antigen binding domain of the ABR, or a membrane-anchored binding molecule that binds to the antigen binding domain of the ABR, such that the ABR, wherein the ABR is expressed on a surface of the viral vector is bound by the co-expressed antigen, fragment thereof, or membrane-anchored binding molecule;
(d) reducing or eliminating expression of the ABR, wherein the ABR is expressed on an envelope of the viral vector;
thereby reducing the insertion of the nucleic acid encoding the ABR into the cell expressing the antigen.

2 more elements

Dependencies are inferred from the claim text.

Methods and compositions to improve the safety and efficacy of cellular therapies

Life of this patent

Methods and compositions to improve the safety and efficacy of cellular therapies

Life of this patent

Abstract

Claims26