Provided is a method for preparation of a composition comprising activated human CD8.sup.+ lymphocytes with phenotype of stem cell-like memory cells and natural killer (NK) lymphocytes. The method entails use of short-term activation of lymphocytes by CD3/CD28 activating agents followed by treatment with DNA-demethylating agent. The invention also provides a version of the method where addition of a CD3/CD28 activating agent is made a few days after initiation of CD4.sup.+ mediated activation of the CD8.sup.+ cells; this step is also disclosed as an improvement of related methods where autologous dendritic cells have been used to activate the lymphocytes. Also provided is a method for treatment of cancer using the cells obtained from the process.

Provided herein is a recombinant cell comprising a deletion of a gene encoding a transporter associated with antigen processing (TAP) protein and mutations in the CD3 epsilon gene and an HLA-A gene. Also provided are systems and methods for screening for alloreactivity and specificity of an immunotherapeutic agent, such as a bispecific T cell engager or an engineered T cell receptor (TCR).

The disclosure relates to a method of treating cancer, and to a population of modified T cells for use in a method of treating cancer.

The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for a) melanoma antigen family A (MAGE A)-3 in the context of HLA-A1 or b) MAGE-A12 in the context of HLA-Cw7. The invention further provides related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells. Further provided by the invention are antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are further provided by the invention.

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.

The methods and compositions disclosed herein relate to the field of cell therapy, and more specifically, to improving CAR and/or TCR function through improvement of the tumor microenvironment via improvement in cytokine signaling. Methods of treating a cancer in a patient are disclosed comprising administering to the patient immune cells expressing a chimeric antigen receptor or T-cell receptor and a membrane bound IL-18. Further disclosed are nucleic acids which encode a membrane bound IL-18 and methods for culturing cells expressing such nucleic acids.

The disclosure relates to a method of treating head and neck cancer, and to a population of modified immunoresponsive cells expressing a heterologous TCR for use in such method.

The disclosure relates to a method of treating gastroesophageal cancer, and to a population of modified T cells expressing a heterologous TCR for use in such method.

The disclosure relates to a method of treating bladder cancer, and to a population of modified immunoresponsive cells expressing a heterologous TCR for use in such method.