Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors or additional cells in combination therapies.

Provided is application of chimeric antigen receptor (CAR)-modified T (CART) cells in preparing drugs for cancer treatment, the CART cells contain an artificially-introduced costimulatory signal transduction domain, and the CART cell does not contain an artificially-introduced first signal transduction domain.

Soluble fusion protein complexes, including domains from IL-15, IL-15 receptor, and αCTLA4 antibody for preventing, reducing the occurrence of, and/or treating cancer or an autoimmune disease or disorder in a subject are provided herein. The methods provided herein include administering to a subject a pharmaceutical composition of a soluble fusion protein complex.

The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.

Genetically programmed microorganisms, such as bacteria or virus, pharmaceutical compositions thereof, and methods of modulating and treating cancers are disclosed.

The present invention provides novel viral vectors for use in human therapy, particularly for use in in the treatment of a disease or disorder which has its origin in the brain or is brain based, particularly a PGRN-associated neurodegenerative disease or disorder including frontotemporal degenerative disease or disorder such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. The invention also provides viral vectors for use in the treatment of brain tumors, particularly brain tumors selected from the group consisting of glioblastoma, glioma, ganglioneuroblastoma, astrocytoma, oligodendroglioma, PNET (primitive neuroectodermal), medulloblastoma, CNS lymphoma, and neuroblastoma, or any other CNS tumor and further in the treatment of brain metastasis, originating from any forms of breast, lung, colon, testicular, renal carcinomas and melanoma, or any other solid tumor, and any hematologic tumor, comprising all forms of leukemia and lymphomas. Further, the viral vectors may be used in the treatment of autoimmune diseases, inflammatory diseases and/or allergic diseases.

Provided are activatable proprotein heterodimers comprising at least two separate polypeptide chains, one chain comprising an IL-2 protein fused to an IL-15 binding protein such as IL-15Rα, and another chain comprising an IL-15 protein fused to an IL-2 binding protein such as IL-2Rα, among other features including binding moieties and cleavable linkers, and related pharmaceutical compositions and methods of use thereof.

Provided are activatable proprotein or procytokine homodimers composed of at least two separate polypeptide chains, each chain comprising a binding moiety such as an Fc region, a cytokine, a cytokine receptor, and at least one a cleavable linker, among other optional features, and related pharmaceutical compositions and methods of use thereof.

The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and/or survival of NK cells.

Embodiments of the present disclosure relate to compositions and methods of enhancing lymphocytes' ability to treat cancer patients. Embodiments relate to a polynucleotide comprising a nucleic acid encoding a chimeric antigen receptor (CAR), a nucleic acid encoding an Oxygen-Dependent Degradation domain (ODD), and a nucleic acid encoding one or multiple sequences of Hypoxia-Response Element (HRE).