A CAR-immunocyte targeting an NKG2D ligand can be used in the preparation of a drug. The drug is used for: (i) removing the senescent cell, the NKG2D ligand in the senescent cell being up-regulated by 2-20 times, preferably 4-15 times, more preferably 10-20 times the normal cell; (ii) delaying individual senescence; and/or (iii) preventing and/or treating age-related diseases. The CAR-immunocyte targeting the NKG2D ligand is capable of specifically removing the senescent cell having high expression of the NKG2D ligand, and has higher in-vivo security.

Provided herein are compositions of NK-92 cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

Modified natural killer (NK) or T cells expressing hematopoietic growth factor receptors are provided. In some aspects, the modified NK cells or T cells express a thrombopoietin receptor, an erythropoietin receptor, or a chimeric polypeptide including an extracellular domain of a thrombopoietin receptor, a transmembrane domain, and an intracellular domain including an interleukin-2 receptor beta intracellular signaling domain. Methods of treating a subject with cancer are also provided, including administering the modified NK cells or T cells to the subject in combination with a thrombopoietin receptor agonist or erythropoietin receptor agonist, and in some example, interleukin-2, particularly reduced or low-dose amounts of IL-2.

The disclosure relates to chimeric antigen receptors and immune effector cells bearing chimeric antigen receptors (CARs). Disclosed herein are improved CARs that are able to recruit Lck and/or and PLC without the need to express CD2, thereby providing efficient CAR function without the risk of CD2-induced fratricide; optionally, the CARs also comprise CD132. Further disclosed herein are improved CARs specific for CD2. Further disclosed herein are improved immune effector cells bearing such improved CARs, therapeutic compositions comprising such improved immune effector cells, and methods for treating cancer using such improved immune effector cells and/or therapeutic compositions.

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

Methods of expanding a natural killer (NK) cell fraction for transplantation into a subject are provided, and particularly, methods for providing transplantable NK cell fractions and protocols for their use, which can be employed for applications in cell transplants and infusions for treatment of cancer and other disease.

Disclosed herein are polypeptides, such as monoclonal antibodies (mAbs) and functional fragments thereof, synthetic antigen-binding proteins such as single-chain variable fragments (scFvs), and chimeric antigen receptors (CARs), that can specifically recognize tumor-associated antigens (TAAs) on cancer cells, for example those that express CD33, FLT3, and CLL-1, useful in the treatment of diseases such as cancer.

Provided are methods and compositions for use in cancer immunotherapies. In various embodiments, the compositions include functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. In various embodiments, 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 in combination therapies.

The use of IL-7R??c agonist peptides in cell manufacturing is disclosed. The IL-7R??c agonist peptides can facilitate the selective growth of immune cell populations. Culture media comprising the IL-7R??c agonist peptides, methods of expanding a target immune cell population, and methods of manufacturing a target immune cell population are disclosed. The enriched immune cell populations can be used in immunotherapy.

The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.