Disclosed are methods of eliminating at least one target cell in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of immune cells, wherein each immune cell of the plurality expresses one or more chimeric ligand receptor(s) (CLR(s)) that each specifically bind to a target ligand on the at least one target cell, wherein specifically binding of the one or more CLR(s) to the target activates the immune cell, and wherein the activated immune cell induces death of the target cell. Exemplary target cells include, but are not limited to, hematopoietic stem cells (HSCs).

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from the 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 in combination therapies.

This disclosure relates to CD8 positive stem-like chronic memory cells for uses in managing diseases and conditions associated with T cell exhaustion and compositions related thereto. In certain embodiments. the CD8 positive cells are PD-1 positive or PD-1 negative. CD62L positive. CD127 positive, and CD44 positive. In certain embodiments. this disclosure relates to methods of treating cancer. chronic viral infections. or chronic diseases comprising administering to a patient in need thereof an effective amount of CD8 positive stem-like chronic memory cells optionally in combination with checkpoint inhibitors. In certain embodiments. the CD8 positive stem-like chronic memory cells are derived from the patient to be treated. are optionally expanded ex vivo, and optionally express a chimeric antigen receptor.

The disclosure relates to immune cells comprising one or more vectors comprising a nucleic acid sequence encoding a chimeric antigen receptor specific for CD19 and a nucleic acid sequence encoding an enhancer of T cell priming (e.g., IL-18), compositions comprising the T cells, and methods of generating and/or using the T cells to treat diseases associated with the expression of CD19.

Aspects of the present disclosure are directed to methods for treating a subject having pancreatic cancer. Certain aspects relate to treatment with cancer immunotherapy, including immune checkpoint blockade therapy. In some cases, a subject has been determined to have or to have had an inflammatory condition, such as pancreatitis. Further aspects relate to methods for identifying a subject as a candidate for an immune checkpoint blockade therapy.

Embodiments of the disclosure include methods and compositions related to targeting of HLA-G-expressing cells with particular engineered receptors. In specific embodiments, NK cells are specifically engineered to bind HLA-G using particular chimeric antigen receptor constructs. In certain embodiments, vectors that express the HLA-G-targeting CARs also express particular a suicide gene and/or one or more particular cytokines.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor agonist.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor agonist.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.