The present application relates generally to genetically modified arenaviruses that are suitable vaccines against neoplastic diseases, such as cancer. The arenaviruses described herein may be suitable for vaccines and/or treatment of neoplastic diseases and/or for the use in immunotherapies. In particular, provided herein are methods and compositions for treating a neoplastic disease by administering a genetically modified arenavirus in combination with an immune checkpoint inhibitor, wherein the arenavirus has been engineered to include a nucleotide sequence encoding a tumor antigen, tumor associated antigen or antigenic fragment thereof.

The invention concerns a novel viral vector with modified viral capsid or viral envelope; a pharmaceutical composition or immunogenic agent or vaccine comprising same; a target cell transformed or transfected with same; a combination therapeutic comprising same; use of same in treatment of cancer, and a method of treating cancer using same.

The disclosure is related to compositions comprising a cell and a spherical nucleic acid (SNA) comprising a nanoparticle, an oligonucleotide on the surface of the nanoparticle, and an antigen; and to methods for production of such compositions and their applications, including but not limited to adoptive cell therapy.

Provided herein, in some embodiments, are methods and composition for treating cancer in a subject. The methods may include administering to the subject a nucleic acid encoding MIP3α fused to a cancer antigen, administering to the subject a CpG oligodeoxynucleotide, administering to the subject interferon alpha (IFNα), and administering to the subject 5-aza-2′-deoxycytidine (Aza), in effective amounts to treat the cancer.

In an aspect, the invention provides therapeutic agents comprising brush polymers that address challenges associated with conventional administration of free therapeutic peptides. In an embodiment, for example, the invention provides brush polymers incorporating one or more therapeutic peptides as side chain moieties. Therapeutic agents of the invention comprising brush polymers include high-density brush polymers including cross-linked brush polymers and brush block copolymers. In an embodiment, brush polymers of the invention exhibit proteolysis-resistant characteristics and maintain their biological function during formulation and administration. The invention also includes methods of making and using therapeutic agents comprising brush polymers.

A set of target peptides are presented by HLA A*0201 on the surface of ovarian cancer cells. They are envisioned to among other things (a) stimulate an immune response to the proliferative disease, e.g., ovarian cancer, (b) function as immunotherapeutics in adoptive T-cell therapy or as a vaccine, (c) facilitate antibody recognition of tumor boundaries in surgical pathology samples, (d) act as biomarkers for early detection and/or diagnosis of the disease, and (e) act as targets in the generation antibody-like molecules which recognize the target-peptide/MHC complex.

Disclosed are means, methods and compositions of matter useful for amplification of adaptive immune responses towards neoplastic tissue. In one embodiment, immunization of a patient is performed by a means comprising of administering either an exogenous vaccine or stimulation of immunogenicity of the tumor so as to cause release of antigens/increased exposure of antigens, thus resulting in an “endogenous” vaccine. Subsequent to vaccination a patient is treated by an immunopheresis procedure, in order to allow for removal of “blocking factors” produced by the tumor or produced by cells programmed by tumors to produce said blocking factors. In one embodiment further immunization is performed subsequent to removal of said blocking factors in order to allow for enhancement of adaptive immune responses.

Spherical Nucleic Acids (SNAs) are chemically well-defined nanoscale architectures comprised of nucleic acids densely arranged around a spherical nanoparticle core in a highly oriented fashion. SNAs are highly modular structures produced by chemical synthesis and programmed assembly, allowing for their rapid modification to incorporate novel viral antigens. The present disclosure provides a SNA comprising (a) a nanoparticle core; (b) a shell of oligonucleotides attached to the external surface of the nanoparticle core, the shell of oligonucleotides comprising one or more immunostimulatory oligonucleotides; and (c) a viral antigen encapsulated in the nanoparticle core.

A composition comprising mesoporous silica rods comprising an immune cell recruitment compound and an immune cell activation compound, and optionally comprising an antigen such as a tumor lysate. The composition is used to elicit an immune response to a vaccine antigen.

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.