The present invention relates to a novel chimeric antigen receptor and to a pharmaceutical composition for preventing or treating containing the same.

Aspects of the present disclosure provide methods for treating a subject having a carcinoembryonic antigen (CEA)-positive tumor using a conditioning regimen (lymphodepleting treatment), which comprises administering one or more doses of a lymphodepleting agent to a subject, and a treatment regimen, which comprises administrating one or more doses of the anti-CEA CAR T cells and/or the ICK proteins to the subject.

Genetically modified cells, including a recombinant nucleic acid expression construct including a first nucleic acid sequence region encoding a chimeric antigen receptor (CAR) that includes an extracellular antigen-binding domain recognizing a carcinoembryonic antigen (CEA) protein, a second nucleic acid sequence region encoding a checkpoint inhibitory molecule, and a third nucleic acid sequence region encoding an immune stimulatory cytokine. In some aspects, the genetically modified cells are T cells or NK cells, preferably cytotoxic T lymphocytes. Anti-CEA CAR-T cells or anti-CEA CAR-NK cells preferentially recognize a membrane-bound CEA protein and express a checkpoint inhibitory molecule and/or an immune stimulatory interleukin in proximity to tumor tissue. Medical use of the cells may relate to treatment of a medical disorder associated with the presence of pathogenic cells expressing CEA, preferably cancer cells, more preferably cancer cells of solid malignancies.

The present disclosure provides methods of producing a modified immune cell responsive to orthogonal cytokine signaling and a modified immune cell produced by said method. The present disclosure further provides a modified immune cell responsive to orthogonal cytokine signaling and methods for treating cancer comprising the modified immune cell.

Aspects of the present disclosure are directed to methods for classification and treatment of small cell lung cancer (SCLC). Certain aspects pertain to treatment of a subject having SCLC using a targeting agent for a cell surface protein, where a targeting agent is selected based on a subtype classification of the SCLC. Disclosed are methods for identifying a subject as having an SCLC subtype (e.g., SCLC-A, SCLC-N, SCLC-P, SCLC-I) and administering a targeting agent configured to target a cell surface protein associated with the identified SCLC subtype. Also disclosed are compositions comprising targeting agents for treatment of SCLC.

The present disclosure provides signal transducer and activator of transcription (STAT)-activated macrophages, compositions comprising STAT-activated macrophages, methods of making STAT-activated macrophages, and methods of treating diseases, e.g., cancer, by administering a therapeutically effective amount of STAT-activated macrophages.

The present invention provides a complex for use in the prevention and/or treatment of cancer, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of cancer, such as a pharmaceutical compositions and vaccines are provided.

The disclosure relates to immune cells comprising systems of two engineered receptors each having a ligand binding domain, collectively designed to target cells identified by loss of heterozygosity and used to treat a disease or disorder, for example, cancer. The disclosure provides immune cells expressing two engineered receptors, methods of making same, and polynucleotides and vectors encoding same.

The present invention discloses a novel switchable dual chimeric antigen receptor-T (sdCAR-T) cell and a construction method and use thereof, which fall within the field of cellular immunotherapy for tumors. The dual chimeric antigen receptor consists of a first chimeric antigen receptor for MSLN and a second chimeric antigen receptor for FITC. A dual-targeted functional T cells regulated by specific exogenous bifunctional molecules is constructed, and the exogenous molecules are used to preliminarily discuss the in vivo and in vitro activity of the dual chimeric antigen receptor-T cell. By means of in vitro and in vivo tests, it is confirmed that the activation mode of the constructed CAR-T cell is controlled by the combination of endogenous tumor antigens and exogenous bifunctional molecules, and this combined regulation mode can significantly improve the safe application of CAR-T cell immunotherapy.

Provided herein are methods employing various fusion constructs in T cell therapy. The fusion constructs allow for one to reduce, to the point of full removal if desired, the use of IL-2 that would otherwise accompany an in vivo T cell therapy.