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.

Chimeric antigen receptors containing CD123 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 presently disclosed subject matter provides methods and compositions for enhancing the immune response toward tumor and pathogen antigens. It relates to immunoresponsive cells comprising two or more chimeric antigen receptors (CARs), wherein the CARs comprise different intracellular signaling domains, in particular, the intracellular signaling domains of the CARs comprise different co-stimulatory molecules.

A novel preparation method for a universal CAR-T cell targeting a T-cell lymphoma cell, the universal CAR-T cell prepared by means of the method and a biological product comprising the universal CAR-T cell. The preparation method for the universal CAR-T cell targeting a T-cell lymphoma cell comprises: obtaining a T cell from a human donor having a healthy lymphatic system, and then disrupting a TRAC genome region and a B2M genome region in the T cell by means of a gene editing technology, so that CAR molecules targeting the T-cell lymphoma cell TCRα/β are stably expressed in the T cell. The universal CAR-T cell targeting a T-cell lymphoma cell prepared by means of the preparation method eliminates the natural TCR expression of a T cell, greatly reduces the graft-versus-host reaction, and meanwhile, also greatly reduces the immunogenicity thereof, and can continuously and efficiently kill the T-cell lymphoma cell.

Provided is a chimeric antigen receptor (CAR) specifically binding to CD138, an immune cell expressing same, and a pharmaceutical composition for the treatment or prevention of cancer including same as an active ingredient. It was confirmed that the CD138 chimeric antigen receptor (CAR)-expressing immune cell of the presently claimed subject matter efficiently exhibits strong cytotoxic ability against CD138-expressing (positive) cancer cells. Accordingly, it is expected that the CD138 chimeric antigen receptor (CAR)-expressing immune cell of the presently claimed subject matter can be utilized for the treatment of CD138-expressing (benign) cancer diseases.

The present invention relates to compositions and methods for treating diseases, disorders or conditions associated with the expression of the glycosyl-phosphatidylinositol (GPI)-linked GDNF family protein -receptor 4 (GFR4).

Provided herein is the use of bryostatin agents to selectively enhance expression, translocation and/or cell surface presentation of an antigen in target cells of interest to modulate immunogenicity of the target cells. Aspects of the methods include, administering an effective amount of a bryostatin agent to a subject to modulate immunogenicity of target cells. The subject methods include a method of treating cancer, including administering to a subject an effective amount of a bryostatin agent to enhance cell surface antigen or neoantigen presentation on target cells of the subject, and administering to the subject a therapeutically effective amount of a therapeutic agent that specifically binds the cell surface antigen to treat the subject for cancer. Aspects of the subject methods also include use of the bryostatin agents to sensitize the target cells to clearance by the subject's immune system.

Provided herein are methods of treating a subject who has multiple myeloma with a ciltacabtagene autoleucel suspension. Also provided are pharmaceutical products containing ciltacabtagene autoleucel suspensions, instructions for use of the ciltacabtagene autoleucel suspensions, and methods for selling a drug product containing ciltacabtagene autoleucel suspensions.

The present invention discloses a nucleic acid molecule for encoding a chimeric antigen receptor targeting CD22 and CD19. The chimeric antigen receptor of the present invention can be used for treatment of CD19.sup.+ and CD22.sup.+ B-cell hematological tumors, as well as combined treatment with CD19 CAR-T cells or CD22 CAR-T cells.

Provided is a bispecific chimeric antigen receptor targeting CD19 and CD22, which comprises extracellular antigen binding domains of heavy-chain variable regions and light-chain variable regions of anti-CD19 and anti-CD22 antibodies. Further provided is a bispecific CAR-T cell targeting CD19 and CD22.