The present invention provides methods compositions and methods of preparing autologous (or allogeneic) B cells that secrete a therapeutic monoclonal antibody of interest or B cells with an altered function.

The disclosure provides CARs (CARs) that specifically bind to CD70. The disclosure further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The disclosure further relates to therapeutic methods for use of these CARs and engineered immune cells comprising these CARs for the treatment of a condition associated with malignant cells expressing CD70 (e.g., cancer).

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric antigen receptors (CAR) and/or genetically modified to reduce potential side effects of cellular immunotherapy. Several embodiments relate to genetic modifications to the immune cells, such as Natural Killer (NK) cells, to reduce, substantially, reduce, or eliminate expression of a marker by the immune cells that would otherwise cause them to be self-targeted by the CAR. In several embodiments, the CAR targets CD70, and in some embodiments is used for renal cell carcinoma immunotherapy.

Provided herein are Claudin 18.2 binding agents and chimeric antigen receptors (CARs) comprising a Claudin 18.2 binding molecule that specifically binds to Claudin 18.2; and immune cells comprising these Claudin 18.2-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using Claudin 18.2-specific CARs and Claudin 18.2 binding agents, and immune cells comprising Claudin 18.2-specific CARs.

The invention provides a chimeric antigen receptor (CAR) having antigenic specificity for CD70, the CAR comprising: an antigen bindingtransmembrane domain comprising a CD27 amino acid sequence lacking all or a portion of the CD27 intracellular T cell signaling domain; a 4-1BB intracellular T cell signaling domain; a CD3? intracellular T cell signaling domain; and optionally, a CD28 intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs 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.

Herein described is a method for treating cancer in a subject by administering a human umbilical cord perivascular cell (HUCPVC) that has been genetically modified to increase the expression of an oligonucleotide or a polypeptide such as an anti-cancer antibody.

The disclosure provides a method of preconditioning a subject for chimeric antigen receptor (CAR) T cell therapy. The method comprises administering to the subject a composition comprising a nanoparticle comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer, at least one day prior to administering CAR T cell therapy to the subject. The disclosure also provides a method of treating a solid tumor in a subject, the method comprising administering to a subject comprising a surface antigen negative solid tumor a first composition comprising the nanoparticle, wherein the nucleic acid within the nanoparticle encodes the surface antigen, and a second composition comprising a CAR T cell that targets the surface antigen.

The disclosure provides a method of preconditioning a subject for chimeric antigen receptor (CAR) T cell therapy. The method comprises administering to the subject a composition comprising a nanoparticle comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer, at least one day prior to administering CAR T cell therapy to the subject. The disclosure also provides a method of treating a solid tumor in a subject, the method comprising administering to a subject comprising a surface antigen negative solid tumor a first composition comprising the nanoparticle, wherein the nucleic acid within the nanoparticle encodes the surface antigen, and a second composition comprising a CAR T cell that targets the surface antigen.

The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of T cell receptors (TCRs) and engineered immunoresponsive cells comprising the same. The novel TCR binds to an antigen in an HLA-independent manner. In certain embodiments, the novel TCR provides enhanced sensitivity for a target gene having a low expression level.

The present invention relates to a chimeric antigen receptor (CAR) comprising an extracellular domain that binds to one or more inflammation associated factor(s), a transmembrane/hinge domain and an intracellular domain. In a specific embodiment, a T regulatory (Treg) cell expressing a construct encoding said CAR which further comprising a Fox3p and a CAR activation-dependent NF-AT promoter that drives the expression of interleukin-10 and TGF-beta. It also relate to the methods of producing the CAR, the Treg cells expressing said CAR and the use of said CAR to treat autoimmune diseases such as transplant rejection, a graft versus host disease (GVHD) and cytokine release syndrome..