Disclosed are antigen delivery systems comprising a nanoparticle, wherein the nanoparticle is surface-modified with a cancer-specific cell targeting peptide and comprises an immunogenic HLA class I restricted peptide, wherein the HLA class I restricted peptide is a vaccine-dependent, immunogenic HLA class I restricted peptide; methods of treating a subject having cancer comprising administering said delivery systems; methods of killing cancer cells comprising contacting cancer cells delivery systems, wherein upon entry of the liposome into the cancer cells, the cancer cells present said peptide from said delivery system, wherein the cancer cells generate an immune response said peptide, and wherein the immune response to said peptide targets and kills the cancer cells presenting the vaccine-dependent, peptide; methods of generating a non-cancer secondary immune response that targets cancer cells comprising administering said delivery systems to a subject having cancer cells.

The present invention relates to pseudotyped retrovirus-like particles or retroviral vectors comprising both engineered envelope glycoproteins derived from a virus of the Paramyxoviridae family fused to a cell targeting domain and fused to a functional domain.

The present invention also relates to the use of said pseudotyped retrovirus-like particles or retroviral vectors to selectively modulate the activity of specific subsets of cells, in particular of specific immune cells. These pseudotyped retrovirus-like particles or retroviral vectors are particularly useful for gene therapy, immune therapy and/or vaccination.

The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and/or NK cells. The methods can include inhibitory RNA molecule(s) and/or engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and/or genetically modified T cells and/or NK cells are provided, such as, for example, those including riboswitches, MRB-CARs, recognition domains, and/or pH-modulating agents.

This document relates to materials and methods for treating cancer. For example, this document provides materials and methods for using PD-L1 targeting domains in bispecific chimeric polypeptides, chimeric transmembrane polypeptides, genetically modified viruses, nucleic acid vectors, and/or fusion-inducing cells to treat cancer.

The present invention provides compositions and methods for transducing cells (e.g. T cells or immune cells). Also provided herein are methods of treating a disease in a subject in need thereof.

The present invention provides a composition comprising i) a pseudotyped retroviral vector particle comprising a) one envelope protein with antigen-binding activity, wherein said envelope protein is a recombinant protein that does not interact with at least one of its original receptors and is fused at its ectodomain to a polypeptide comprising an antigen binding domain specific for CD62L, and wherein said envelope protein is protein G, HN or H derived from the Paramyxoviridae family, b) one envelope protein with fusion activity derived from the Paramyxoviridae family, and T cells expressing CD62L. Alternatively, when said polypeptide comprising an antigen binding domain is specific for a tag of a tagged polypeptide instead of the antigen binding domain specific for CD62L, wherein said tagged polypeptide binds specifically to CD62L, then the composition comprises further said tagged polypeptide.

The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and/or NK cells. The methods can include inhibitory RNA molecule(s) and/or engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and/or genetically modified T cells and/or NK cells are provided, such as, for example, those including riboswitches, MRB-CARs, recognition domains, and/or pH-modulating agents.

The present invention provides a composition comprising i) a pseudotyped retroviral vector particle or virus-like particle thereof comprising a) one envelope protein with antigen-binding activity, wherein said envelope protein is a recombinant protein that does not interact with at least one of its native receptor(s) and is fused at its ectodomain to a polypeptide comprising an antigen binding domain specific for a tag of a tagged polypeptide, and wherein said envelope protein is protein G, HN or H derived from the Paramyxoviridae family, and b) one envelope protein with fusion activity derived from the Paramyxoviridae family, and ii) said tagged polypeptide, wherein said tagged polypeptide binds specifically to an antigen expressed on the surface of a target cell, thereby transducing the target cell with said retroviral vector particle or thereby inducing uptake of the virus-like particle into the target cell. A pharmaceutical composition thereof and an in vitro method for transduction of targets cells with said vector particle are also disclosed.

The present invention provides compositions and methods for transducing cells (e.g. T cells or immune cells). Also provided herein are methods of treating a disease in a subject in need thereof.

The present disclosure provides, at least in part, methods and compositions for in vivo fusosome delivery. In some embodiments, the fusosome comprises a combination of elements that promote specificity for target cells, e.g., one or more of a fusogen, a positive target cell-specific regulatory element, and a non-target cell-specific regulatory element. In some embodiments, the fusosome comprises one or more modifications that decrease an immune response against the fusosome.