The disclosure provides immune cells comprising a first activator receptor specific to mesothelin and a second inhibitory receptor specific to a ligand that has been lost in a mesothelin-positive cancer cell, and methods of making and using same for the treatment of cancer.

Nanoparticles to treat autoimmune diseases and HIV infection are provided. The nanoparticles comprise a biocompatible polymer and a complex, wherein the complex is a major histocompatibility complex (MHC) class I antigen E (HLA-E) linked to a peptide, and wherein the HLA-E-peptide complex is linked to the surface of the nanoparticle. The present invention also relates to methods for treating autoimmune diseases and HIV infection.

Embodiments of the disclosure concern methods and compositions for immunotherapy for human papillomavirus infection and diseases associated therewith. In specific embodiments, methods concern production of immune cells that target one or more antigens of HPV16 and/or HPV18, including methods with stimulation steps that employ IL-7 and IL-15, but not IL-6 and/or IL-12. Other specific embodiments utilize stimulations in the presence of certain cells, such as costimulatory cells and certain antigen presenting cells.

The invention provides methods of making immune effector cells (for example, T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions generated by such methods.

Methods for preparing T cells or NK cells expressing a chimeric antigen receptor (CAR) is described. The methods entail: isolating a population of T cells, generating induced pluripotent stem cells (iPSCs) from the T cells, introducing a nucleic acid molecule encoding a CAR into the iPSCs to create CAR iPSCs; and differentiating the CAR iPSCs into CAR T cells or CAR NK cells.

The present invention provides improved and/or shortened processes and methods for reprogramming TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy. Such reprogrammed TILs find use in therapeutic treatment regimens.

The present disclosure provides recombinant T cells that include a vector encoding one or more of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC1α), mitochondrial transcription factor A (Tfam), GA binding protein transcription factor alpha subunit (GABPA), and estrogen-related receptor alpha (ERRα). Such recombinant T cells can also include a chimeric antigen receptor (CAR) or a recombinant T cell receptor (TCR). Methods of using these recombinant T cells in cancer immunotherapy are provided. Also provided are kits and compositions that can be used with such methods.

This invention relates to the expansion of non-haematopoietic tissue-resident γδ T cells in vitro by culturing lympho-cytes obtained from non-haematopoietic tissue of humans or non-human animals in the presence of interleukin-2 (IL-2) and/or inter-leukin-15 (IL-15) and the absence of TCR activation or co-stimulation signals, without any direct contact with stromal or epithelial cells. Methods of non-haematopoietic tissue-resident γδ T cell expansion are provided, as well as populations of non-haematopoietic tissue-resident γδ T cells and uses thereof.

Methods are disclosed for treating a subject with a tumor. These methods include administering to the subject a therapeutically effective amount of CD8.sup.+CD39.sup.+CD103.sup.+ T cells. Methods also are disclosed for isolating a nucleic acid encoding a T cell receptor (TCR) that specifically binds a tumor cell antigen. These methods include isolating CD8.sup.+CD39.sup.+CD103.sup.+ T cells from a sample from a subject with a tumor expressing the tumor cell antigen, and cloning a nucleic acid molecule encoding a TCR from the CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In addition, methods are disclosed for expanding CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In additional embodiments, methods are disclosed for determining if a subject with a tumor will respond to a checkpoint inhibitor. The methods include detecting the presence of CD8.sup.+CD39.sup.+CD103.sup.+ T cells in a biological sample from a subject.

Provided are methods of producing an isolated population of T cells for adoptive cell therapy. Also provided are related isolated populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer, infections, and autoimmune conditions in a patient.