The present disclosure provides compositions and methods for treating diseases associated with expression of CD19 and/or CD22, e.g., by administering a recombinant T cell or natural killer (NK) cell comprising a CD22 CAR and a CD19 CAR as described herein. The disclosure also relates to CAR molecules specific to CD22 and/or CD19, methods of making a cell comprising the same and vectors encoding the same.

Chimeric antigen receptors containing CD19/CD22 or CD22/CD19 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

The present disclosure relates to CD19/22 CAR T-cell products and methods for treating high risk or relapsed CD19+ or CD22+ haematological malignancies.

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.

A method for producing T cells modified by a chimeric antigen receptor, comprising: transfecting K562 cells with shFPPS targeted to FPP synthase by means of a lentiviral vector, such that the expression of FPPS in the K562 cells is lowered and a K562-shFPPS cell line with reduced FPPS expression is constructed; adding the K562-shFPPS cell line into a T cell culture system for co-culturing with the T cells, wherein it is found that the K562-shFPPS cell line can facilitate in vitro differentiation and proliferation of the T cells; and adding a CAR-expressing lentiviral vector to the T cell culture system comprising the cell line for co-culturing, wherein it is found that the K562-shFPPS cell line can further effectively improve the transfection rate of CAR genes. The provided solution effectively overcomes the technical challenge of the large-scale production of CAR- T cells, and has a good application prospect.

Compositions for the treatment of cancer that include CAR T cells in which expression of FOXO3 expression is silenced are disclosed in various aspects. In various other aspects, methods for preventing or delaying a development of dysfunction in a CAR T cell associated with chronic antigen stimulation are described that include silencing the expression of FOXO3 by the CAR T cell.

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

Multiplex base edited chimeric antigen receptor (CAR)-expressing immune effector cells (e.g., T or NK cells) having increased resistance to development of an exhausted phenotype (e.g., increased cytotoxicity, proliferation, survival, and/or cytokine production) after repeated or continuous stimulation by an antigen relative to unedited CAR immune effector cells, compositions containing the cells, methods for the preparation of the cells, and methods for use of the cells in treating a disease or disorder (e.g., an autoimmune disorder or a neoplasia, such as a leukemia).

The present invention concerns new engineered immune cells expressing two CARs directed against two different targets, polynucleotides for preparing said immune cells, pharmaceutical compositions comprising said immune cells, and the use of said immune cells in the treatment of cancers.