Provided herein are systems comprising one or both of cytokines and/or synthetic pathway activators. Also provided herein are systems comprising one or more suppressors of gene expression, and one or both of cytokines and/or synthetic pathway activators. Also provided are systems of chimeric priming receptors that bind ALPG and/or ALPP, chimeric antigen receptors that bind MSLN, and at least one of one or more suppressors of gene expression, and/or one or both of cytokines and/or synthetic pathway activators; cells expressing such systems; and methods of use thereof.

Provided herein are anti-TSLP antibodies or antigen-binding fragments thereof, isolated poly nucleotides encoding the same, pharmaceutical compositions comprising the same, and the uses thereof.

Provided is a membrane surface protein containing a GPI anchor region. Specifically, provided are a fusion protein comprising a functional domain and a GPI anchor region, and the use thereof. The fusion protein can effectively activate and proliferate immune cells, and improve the effector function of immune cells.

Compositions and methods far delivering immune modulatory molecules to result in a therapeutic effect are disclosed. The compositions and methods use stably integrating lentiviral delivery systems. The methods are useful for therapeutically and prophylactically treating cancer such as leukemia.

This invention relates to the field of therapeutics. Most specifically invention provides methods of generating in vitro engineered immune cells conditionally expressing interleukin-12 (IL-12) and one or more immunomodulators under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals.

Provided herein are compositions and methods for the treatment of cancers using modified TILs, wherein the modified TILs include one or more immunomodulatory agents (e.g., cytokines) associated with their cell surface. The immunomodulatory agents associated with the TILs provide a localized immunostimulatory effect that can advantageously enhance TIL survival, proliferation and/or anti-tumor activity in a patient recipient. As such, the compositions and methods disclosed herein provide effective cancer therapies.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing mono- and/or bi-specific chimeric antigen receptors (CAR) with anti-CD133 and anti-EGFR antigen binding domains, and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

Provided herein are chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.

Provided herein are chimeric antigen receptors (CARs) with binding specificity for CD123. Nucleic acids, expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are also disclosed, and methods including the treatment of a hematopoietic malignancy or premalignancy characterized by the expression of CD123, e.g., leukemias such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Provided herein, among other things, are polynucleotides comprising a nucleic acid encoding an anti-human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR) and natural killer cells expressing the polynucleotides.