The invention broadly comprises a chemical composition including a plurality of cholesteryl esters arranged to form a vesicle. In several embodiments, all of the plurality of cholesteryl esters have a same molecular length, which in some embodiments provides a vesicle having a generally smooth outer surface, while in other embodiments, a portion of the plurality of cholesteryl esters have different molecular lengths, which in some embodiments provides a vesicle having a generally irregular outer surface. In yet further embodiments, a shape of the vesicle is selected from the group consisting of spherical, oval, disc-like, tubular and polyhedral shapes, and in yet other embodiments, a wall of the vesicle is selected from the group consisting of a monolayer and a bilayer. In still further embodiments, the chemical composition further includes a polyethylene glycol coat of mixed polymer size. In some embodiments, the plurality of cholesteryl esters include at least two different cholesteryl esters, and in some of these embodiments, the at least two different cholesteryl esters are selected from the group consisting of cholesteryl myristate, cholesteryl laurate, cholesteryl dodeconate, cholesteryl palmitate, cholesteryl arachidonate, cholesteryl behenate, cholesteryl linoleate, cholesteryl linolenate, cholesteryl oleate and cholesteryl stearate.

Materials and methods for modulating activity of kinases such as AMPK and mTOR via the deubiquitinase, USP10, are provided herein. Also provided are materials and methods for treating clinical conditions mediated at least in part by such kinases, including obesity, diabetes, metabolic syndrome, and some cancers.

A preparation and an application of a chimeric antigen receptor immune cell constructed on the basis of granzyme B are provided, including, a granzyme B (GrB)-based modified chimeric antigen receptor (CAR), the CAR containing an extracellular binding domain, and the extracellular binding domain being capable of specifically targeting heat shock proteins. The CAR immune cell acts by means of binding of a ligand and a receptor, and has relatively high targeting specificity and relatively better safety.

Provided are combination therapies for treating and preventing relapse of a tumor and infectious diseases in a subject, as well as methods for use thereof. The combination therapies comprise an Hsp70 based pharmaceutical ingredient and at least one further immunotherapeutic agent that specifically inhibits and/or preferably binds to an immune checkpoint molecule or tumor immune microenvironment immune regulator. Furthermore, a kit and methods of using the combination therapies of the invention are described.

The invention broadly comprises a chemical composition including a plurality of cholesteryl esters arranged to form a vesicle. In several embodiments, all of the plurality of cholesteryl esters have a same molecular length, which in some embodiments provides a vesicle having a generally smooth outer surface, while in other embodiments, a portion of the plurality of cholesteryl esters have different molecular lengths, which in some embodiments provides a vesicle having a generally irregular outer surface. In yet further embodiments, a shape of the vesicle is selected from the group consisting of spherical, oval, disc-like, tubular and polyhedral shapes, and in yet other embodiments, a wall of the vesicle is selected from the group consisting of a monolayer and a bilayer. In still further embodiments, the chemical composition further includes a polyethylene glycol coat of mixed polymer size. In some embodiments, the plurality of cholesteryl esters include at least two different cholesteryl esters, and in some of these embodiments, the at least two different cholesteryl esters are selected from the group consisting of: cholesteryl myristate, cholesteryl laurate, cholesteryl dodeconate, cholesteryl palmitate, cholesteryl arachidonate, cholesteryl behenate, cholesteryl linoleate, cholesteryl linolenate, cholesteryl oleate and cholesteryl stearate.

The present invention is directed to the field of immunotherapy. Specifically, the invention provides improved cell compositions and methods for adoptive cell therapy, useful in the treatment of cancer. More specifically, embodiments of the invention employ the use of cell compositions comprising a high proportion of activated cytotoxic CD8.sup.+ cells and in particular CD8.sup.+NKG2D.sup.+granzyme-B.sup.+ cells characterized by enhanced cytotoxicity, to processes for their preparation from peripheral blood mononuclear cells (PBMC), and to their use in cancer management.

The disclosure relates to a fusion protein comprising a colony stimulating factor 1 (CSF1) portion and a granzyme B portion, and polynucleotide sequence encoding the fusion protein. The disclosure also relates to a virus comprising the polynucleotide, and a T cell expressing the polynucleotide. The disclosure further relates to a method of treating a disease in an individual by administering the fusion protein, the polynucleotide, the oncolytic virus, or the T cell, and to a composition for use in method.

The invention is directed to methods and compositions for cell-based targeted delivery of predetermined compounds to a population of target cells. In some embodiments, methods of the invention include providing cytotoxic lymphocytes genetically modified to produce and sequester in lytic granules fusion proteins comprising a granzyme, or other effector agent, and a predetermined protein, so that upon specific contact of the cytotoxic lymphocytes with the target cells, the granzyme-perforin pathway of the cytotoxic lymphocytes is activated, leading to the delivery of the fusion protein to the cytosols of the target cells.

Disclosed herein are methods, systems and devices to model adaptive immune responses and develop and/or test improved antibodies, vaccines, and other therapeutic agents. The adaptive immune responses can be modeled using lymphoid tissue derived from a subject. The methods, systems and devices disclosed herein can comprise modified T-cells.

A polypeptide having a serine protease variant of the human granzyme B set forth by SEQ ID NO: 1, wherein the serine protease variant has at least 95% identity to SEQ ID NO: 1 and has a substitution at the position that corresponds structurally or by amino acid sequence homology to position Arg201 of SEQ ID NO: 1, and wherein the serine protease variant has activity to cleave the motif Ile-Glu-Thr-Asp.