Compositions and methods are provided for treating lymphoma in an individual by targeting engineered phagocytes to lymphoma cells. In particular, the phagocytes provided for administration to an individual, who has lymphoma, are engineered to express a chimeric antigen receptor (CAR) that specifically binds to an antigen present on lymphoma cells. The CAR localizes the engineered phagocytes to sites where lymphoma cells are present. In some embodiments, phagocytic activity of the phagocytes is enhanced by further engineering the phagocytes to express a hyperactive Rac GTPase.

CAR Tregs and Tregs are provided which are both conversion-resistant and condition-resistant. The Treg cells are engineered such that they are deficient in or substantially devoid of a cell-surface marker or antigen.

Provided are a chimeric antigen receptor immune cell, and a preparation method therefor and an application thereof. The surface of the chimeric antigen receptor immune cell expresses a receptor targeting a specific antigen, and also expresses a signal conversion protein. The signal conversion protein is a fusion protein containing a dominant negative receptor TGFBR2 extracellular element and an IL-7R intracellular element. The chimeric antigen receptor immune cell can further convert, by means of the signal conversion protein, the inhibitory signal of a TGF- immunosuppressive factor in a tumor microenvironment that is not conducive to the survival of immune cells into a cytokine activation signal, thereby significantly enhancing the survival of the immune cells and having a more sustained tumor killing effect.

The invention features a method for treating graft versus host disease in a human, including administering to said human a therapeutically effective amount of a cell including a chimeric antigen receptor (CAR) which is specifically directed against an immune checkpoint molecule.

The technology described herein is directed to targeting molecules that bind to one or more transmembrane molecules expressed in tumor vascular endothelial cells and that are capable of targeting an agent that induces cell death, for example, immunogenic or non-immunogenic cancer cell death. In another aspect, described herein are methods of treating a subject having cancer comprising administering said targeting molecules and agents, and, in certain embodiments, enhancing the immunogenic response to the cancer, for example, by enhancing intratumoral infiltration of T cells.

Disclosed are receptor cytokine switches, immune cells containing them, and uses thereof for controllable adoptive cell therapy.

Embodiments of the disclosure encompass particular chimeric antigen receptor constructs that comprise optionally a hinge, one of the CD28 transmembrane domain or the DAP10 transmembrane domain, DAP10 costimulatory domain, and CD3zeta. In particular embodiments, the chimeric antigen receptor is expressed by natural killer (NK) cells, and in some cases the NK cells are further modified, such as to express one or more cytokines and optionally a suicide gene.

The present disclosure provides chimeric antigen receptors that bind to Axl and Ror2, and conditionally active chimeric antigen receptors (CARs) that recognize Axl and Ror2. Furthermore, provided herein are nucleic acids encoding these CARs and methods of making and using the CARs, including methods of treating cancer, especially cancers that express Axl and/or Ror2, such as renal cell carcinoma. The present disclosure provides cells genetically modified to produce the CARs.

Provided are chimeric antigen receptors having the hinge, transmembrane region, and/or intracellular domain of LILRB1, or functional fragments or variants thereof. Also provided herein are cells comprising the LILRB1 based receptors, and methods of making and using same.

The present invention relates to a cell comprising a chimeric antigen receptor (CAR) and a constitutively active or inducible Signal Transducer and Activator of Transcription (STAT) molecule.