Abstract: Provided herein are methods for the activation and expansion of genetically-modified Tcells, such as tumor infiltrating lymphocytes. In some cases, cells of the embodiments can be used for the therapeutic treatment of human diseases, such as cancer.

Abstract: The present disclosure relates to an engineered T-cell Receptors (TCRs) capable of binding to an epitope of an epidermal growth factor receptor (EGFR) comprising a T790M mutation presented on human leukocyte antigen-A (HLA-A)*02:01, wherein the epitope comprises the amino acid sequence of MQLMPFGCLL (SEQ ID NO: 1). Also disclosed are Tcell and BiTE therapies comprising the same, and methods of treating EGFR-TKI resistant lung cancers using the same.

Abstract: In one aspect, disclosed herein are novel multimeric costimulatory agonistic constructs comprising said monomers for expanding tumor infiltrating lymphocytes (TILs) in vitro or ex vivo said methods comprising obtaining TILs and culturing the TILs in media comprising one or more multimeric costimulatory agonists.

Abstract: Disclosed herein are immune effector cells for use in adoptive cell transfer that have chemically- or genetically-inhibited PDHB (Pyruvate dehydrogenase E1 subunit beta) expression or activity. Also disclosed are methods of inhibiting or ablating PDHB expression in immune effector cells ex vivo and methods of using these cells to treat subjects with cancer. In some embodiments, the immune effector cells are further treated with a TIMS inhibitor or genetically engineered to ablate TIM3 expression. In some embodiments, the immune effector cells are further treated with a LAGS inhibitor or genetically engineered to ablate LAG3 expression. In some cases, the PDHB gene is disrupted by insertion of the gene encoding the chimeric receptor into the PDHB gene loci of the cell. Therefore, disclosed herein is a chimeric cell expressing a chimeric receptor.

Abstract: Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of a TLR agonist and a chimeric CD154 polypeptide. Also provided herein are methods of enhanced immune function.

Abstract: As disclosed herein, high expression of the inhibitory ligands Galectin-3 (LAG-3 ligand), Galectin-9 (Tim-3 ligand), HMGB1 (Tim-3 ligand), CD112 (CD112R ligand) and TNFSF10 (DR5 ligand) in the microenvironment of triple negative breast cancer cells is inhibitory for T-cells. Therefore, disclosed herein is a chimeric receptor comprising an extracellular domain of TIM-3, LAG-3, CD112R or DR5 and transmembrane and intracellular domain of a pro-inflammatory interleukin and/or a co-stimulatory domain. Also disclosed is an immune effector cell engineered to express a chimeric antigen receptor (CAR) polypeptide and the disclosed chimeric receptor. Also disclosed is a method of providing an anti-cancer immunity in a subject with a MUC1-expressing cancer, the method comprising administering to the subject an effective amount of the disclosed immune effector cell, thereby providing an anti-tumor immunity in the subject.

Abstract: This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize EGFR neoantigens comprising L858R mutations and restricted to HLA class I A31 and A33 allotypes. Accordingly, aspects of the disclosure relate to a polypeptide comprising an antigen binding variable region comprising the amino acid sequence of a CDR3 of the disclosure or an amino acid sequence with at least 80% sequence identity to a CDR3 of the disclosure.

Abstract: This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize EGFR neoantigens comprising L858R mutations and restricted to HLA class I A11 allotype. Accordingly, aspects of the disclosure relate to a polypeptide comprising an antigen binding variable region comprising the amino acid sequence of a CDR3 of the disclosure or an amino acid sequence with at least 80% sequence identity to a CDR3 of the disclosure.

Abstract: Embodiments of the disclosure encompass methods and compositions related to cell therapy treatment, including for cancer. In specific embodiments, the disclosure concerns adoptive cell therapy cancer treatment in which tumor-1 infiltrating lymphocytes and/or engineered T cells are modified to increase their efficacy as a cancer treatment. In specific cases, the cells are engineered for knock out of one or more genes, such as Signaling Threshold Regulating Transmembrane Adaptor 1 (SIT1), Bone Marrow Stromal Cell Antigen 2 (BST2), and/or programmed cell death protein 1 (PD-1).

Abstract: The present invention discloses a mouse-human chimeric antibody preferably recognizes the MUC1 glycopeptide epitope RPAPGS(GalNAc)TAPPAHG (SEQ ID NO.: 34) on the surface of cancer cells, and the encoding sequences, wherein the monoclonal antibody having a light chain and a heavy chain. Moreover, the present invention provides humanized light and heavy chains, and the encoding sequences. The results of paired expression show that humanized antibodies also recognize the MUC1 glycopeptide epitope RPAPGS(GalNAc)TAPPAHG (SEQ ID NO.: 34) on the surface of cancer cells, and show the same specificity as the parental antibody.

Abstract: Provided herein are methods for the activation and expansion of genetically-modified Tcells, such as tumor infiltrating lymphocytes. In some cases, cells of the embodiments can be used for the therapeutic treatment of human diseases, such as cancer.

Abstract: Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of at least one immune checkpoint inhibitor and a chimeric CD 154 polypeptide. Also provided herein are methods of enhanced immune function.

Abstract: Embodiments of the disclosure provide methods and compositions that facilitate cancer treatment including at least because they concern therapies that circumvent the tumor microenvironment. In specific embodiments, compositions are utilized for therapy that utilize tumor-infiltrating lymphocytes and/or engineered T cells that are protected from immunosuppression from the tumor microenvironment because they are engineered to have reduced or eliminated expression of transforming growth factor-beta receptor 2 and/or I-cell-Ig-and-ITIM-domain and/or CD7 genes.

Abstract: The present disclosure relates to compositions and methods for treating cancer, more specifically to methods and compositions comprising a Topoisomerase I inhibitor and an ?-PD-L1 antibody

Abstract: The present disclosure relates to methods of identifying RNA-edited peptides. In an aspect, the identified peptides are capable of eliciting immune responses in individuals or patients. The present disclosure further relates to RNA-edited peptide sequences identified by methods described herein. In a further aspect, the disclosure provides for methods of treating cancer in individuals or patients by utilizing the methodology described herein.

Abstract: Provided are SLC45A2 peptides that bind to MHC I (HLA-A2) on melanoma cells or other antigen-presenting cells and are recognized by T-cell receptors on T cells. The SLC45A2 peptides may be therapeutically used to treat a cancer, such as a cutaneous melanoma, uveal melanoma, a mucosal melanoma, or a metastatic melanoma. Methods for expanding a population of T cells that target SLC45A2 are also provided.

Abstract: The present disclosure relates to compositions and methods for treating cancer, more specifically to methods and compositions comprising a Topoisomerase I inhibitor and an ?-PD-L1 antibody.

Abstract: Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of a TLR agonist and a chimeric CD154 polypeptide. Also provided herein are methods of enhanced immune function.

Abstract: Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of at least one immune checkpoint inhibitor and a chimeric CD 154 polypeptide. Also provided herein are methods of enhanced immune function.

Abstract: The present invention discloses a mouse-human chimeric antibody preferably recognizes the MUC1 glycopeptide epitope RPAPGS(GalNAc)TAPPAHG on the surface of cancer cells, and the encoding sequences, wherein the monoclonal antibody having a light chain and a heavy chain. Moreover, the present invention provides humanized light and heavy chains, and the encoding sequences. The results of paired expression show that humanized antibodies also recognize the MUC1 glycopeptide epitope RPAPGS(GalNAc)TAPPAHG on the surface of cancer cells, and show the same specificity as the parental antibody.