The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

Genetically engineered immune cells such as T cells having a disrupted CD83 gene and optionally expressing a chimeric antigen receptor (CAR) and therapeutic applications thereof. Such genetically engineered immune cells may further comprise a disrupted TRAC gene, a disrupted β2M gene, or a combination thereof.

The present invention provides a combined chimeric antigen receptor targeting CD19 and CD20 and application thereof. Specifically, the present invention provides a combined chimeric antigen receptor targeting CD19 and CD20, which comprises a scFv targeting CD19 and CD20, a hinge region, a transmembrane region, and an intracellular signaling domain. The present invention provides a nucleic acid molecule encoding the chimeric antigen receptor and a corresponding expression vector, a CAR-T cell, and applications thereof. The experimental results show that the chimeric antigen receptor provided by the present invention shows extremely high killing ability against tumor cells. The chimeric antigen receptor of the present invention targets CD19 and/or CD20 positive cells and can be used to treat CD19 and/or CD20 positive B-cell lymphoma, leukemia and other diseases.

The present disclosure provides methods of treating cancer or light chain amyloidosis in a subject in need thereof comprising administering a combination therapy comprising an effective amount of Form A of nirogacestat dihydrobromide and a B-cell maturation antigen (BCMA)-directed therapy to the subject and the uses thereof.

The present disclosure relates to an engineered immune cell and use thereof. The present disclosure provides an engineered immune cell comprising a CAR or engineered TCR, which CAR or engineered TCR can comprise a first antigen binding domain and a second antigen binding domain. The engineered immune cells of the present disclosure, when administered into a subject, can inhibit the host immune cells such as T cells and/or NK cells and enhance the survival and persistence of the engineered immune cells in vivo, thereby exhibiting more effective tumor killing activity.

Provided herein are methods for expanding NK cells expressing chimeric antigen receptors and/or T cell receptors. Further provided are methods for treating diseases by administering the CAR NK cells.

The invention provides antibodies, antibody-drug conjugates, bispecific T cell engagers (BiTEs), and chimeric antigen receptors (CARs) that target transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Such antibodies, antibody-drug conjugates, BiTEs, and CARs can be used, e.g., in methods for treating a cancer (e.g., multiple myeloma), an autoimmune disorder (e.g., characterized by a high titer of antibodies contributing to the disorder), or a plasma cell disease disorder (e.g., plasma cell dyscrasias) in a subject in need thereof.

Provided are methods and compositions directed to the treatment of an individual having cancer by (i) administering to the individual an adoptive cellular immunotherapy composition comprising CAR T cells and (ii) administering to the individual an interleukin-15 receptor agonist, such as, for example, a long-acting interleukin-15 receptor agonist.

Acute lymphoblastic leukemia (ALL) has not benefited from innovative immunotherapies, mainly because of the lack of actionable immune targets. Novel tumor-specific antigens (TSAs) specifically expressed by ALL cells are described herein. Most of the TSAs described herein derives from aberrantly expressed unmutated genomic sequences, such as intronic and intergenic sequences, which are not expressed in normal tissues. Nucleic acids, compositions, cells, antibodies and vaccines derived from these TSAs are described. The use of the TSAs, nucleic acids, compositions, antibodies, cells and vaccines for the treatment of leukemia such as ALL is also described.

There are provided, inter alia, compositions and methods for treatment of cancer. The methods include administering to a subject in need a therapeutically effective amount of a Bruton's tyrosine kinase (BTK) antagonist and a ROR-1 antagonist. Further provided are pharmaceutical compositions including a BTK antagonist, ROR-1 antagonist and a pharmaceutically acceptable excipient. In embodiments, the BTK antagonist is ibrutinib and the ROR-1 antagonist is cirmtuzumab.