The present disclosure is directed towards genetically engineered TCR-T cells to recognize tumor antigens and simultaneously secrete a binding protein that blocks an immune checkpoint molecule and TGF. These engineered T cells demonstrate stronger antitumor response and reduced T cell exhaustion. The present disclosure provides immunotherapy against HPV- or EBV-positive cancers, among others.

Provided herein are improved methods of treating cancer in humans by activating resident memory T cells in tumors using one or more antigenic peptides.

Provided herein are improved methods of treating cancer in humans by activating resident memory T cells in tumors using one or more antigenic peptides.

This disclosure relates, inter alia, to compositions comprising and methods making and using T cells expressing both a chimeric antigen receptor (CAR) targeted to HIV and a T cell receptor targeted to cytomegalovirus (CMV).

This disclosure relates, inter alia, to compositions comprising and methods making and using T cells expressing both a chimeric antigen receptor (CAR) targeted to HIV and a T cell receptor targeted to cytomegalovirus (CMV).

The present invention provides a method for the expansion of HPV immunogen specific T cells, comprising the steps of: i. providing a phagocytosable particle comprising a core and a human papillomavirus (HPV) immunogen tightly associated to the core; wherein the HPV immunogen has an amino acid sequence that corresponds to the amino acid sequence of a HPV protein, or has an amino acid sequence that corresponds to an amino acid sequence of a part of a HPV protein; ii. providing APCs; iii. contacting the phagocytosable particle comprising a core and a HPV immunogen with the APCs from step ii in vitro, and under conditions allowing phagocytosis of the HPV immunogen by the APCs; iv. providing T-cells that have been harvested from a subject; v. contacting the T-cells with the APCs from step iii) in vitro, and under conditions allowing specific activation of HPV immunogen specific T-cells. The invention further provides an expanded population of therapeutically useful T-cells and their use in the treatment or prevention of cancer, particularly HPV positive cancers.

The present invention provides a method for the expansion of HPV immunogen specific T cells, comprising the steps of: i. providing a phagocytosable particle comprising a core and a human papillomavirus (HPV) immunogen tightly associated to the core; wherein the HPV immunogen has an amino acid sequence that corresponds to the amino acid sequence of a HPV protein, or has an amino acid sequence that corresponds to an amino acid sequence of a part of a HPV protein; ii. providing APCs; iii. contacting the phagocytosable particle comprising a core and a HPV immunogen with the APCs from step ii in vitro, and under conditions allowing phagocytosis of the HPV immunogen by the APCs; iv. providing T-cells that have been harvested from a subject; v. contacting the T-cells with the APCs from step iii) in vitro, and under conditions allowing specific activation of HPV immunogen specific T-cells. The invention further provides an expanded population of therapeutically useful T-cells and their use in the treatment or prevention of cancer, particularly HPV positive cancers.

Provided methods of obtaining a plurality of T cell receptors specifically recognizing a target tumor antigen peptide from an individual that has clinically benefitted from an immunotherapy, such as Multiple Antigen Specific Cell Therapy. Also provided tumor-specific TCRs, engineered immune cells expressing the TCRs and methods of treating a disease using the engineered immune cells.

Provided methods of obtaining a plurality of T cell receptors specifically recognizing a target tumor antigen peptide from an individual that has clinically benefitted from an immunotherapy, such as Multiple Antigen Specific Cell Therapy. Also provided tumor-specific TCRs, engineered immune cells expressing the TCRs and methods of treating a disease using the engineered immune cells.

The disclosure relates to delivery systems, and corresponding methods, for selecting and delivering an allogeneic T-cell line for administration to a patient, e.g., according to the HLA profile of the patient's somatic or diseased cells.