Abstract: The invention provides compositions and methods for delivering agents to localized regions, tissues, or organs in vivo by conjugating agent-loaded nanoparticles to cells having homing capability. The agents may be therapeutic or diagnostic agents such as cancer chemotherapeutic agents and imaging agents respectively.

Abstract: The present invention provides a conjugate comprising an albumin binding peptide and a cargo, compositions for directing cargos to the lymphatic system, and vaccines. The methods of the invention can be used to increase an immune response, or to treat cancer or an infectious disease.

Abstract: The present disclosure is directed, in some embodiments, to methods and compositions of comprising a cell having a non-internalizing receptor, and a nanoparticle surface-modified with a ligand that binds to the non-internalizing receptor.

Abstract: Disclosed herein are lipid nanoparticles comprising 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000](DSPE-PEG2000), compositions including such lipid nanoparticles, and methods of treatment using such lipid nanoparticles and compositions.

Abstract: The present invention provides a method of treating cancer with a combination of IL-2 (e.g., extended-PK IL-2), an integrin-binding-Fc fusion protein, and a cancer vaccine. The methods of the invention can be used to treat a broad range of cancer types.

Abstract: The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

Abstract: Disclosed herein are methods and compositions for treating a subject having or at risk of having an HIV infection. Disclosed herein are peptide immunogens and nucleic acids that have epitopes in which mutations are most likely to have deleterious effects on the HIV virus. An algorithm is disclosed for the selection of the epitopes based on the HIV fitness landscape, and it accounts for the effect of coupling mutations.

Abstract: The present disclosure relates to a device, comprising a base and a plurality of microneedles attached to the base, wherein each microneedle has an outer surface; the outer surface of at least one microneedle being coated with a composition comprising at least one polymer and least one Peptide Nucleic Acid (PNA). The present disclosure additionally relates to a method of detecting an analyte in interstitial fluid (ISF), comprising contacting the device to a subject, for example, to human skin.

Abstract: The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.

Abstract: Provided herein are methods for stimulating an immune response to a target cell population or a target tissue in a subject by administering to the subject a composition comprising an amphiphilic ligand conjugate. Such an amphiphilic ligand conjugate can comprise a lipid, one or more cargos (e.g., a CAR ligand, a chimeric cytokine receptor target, a chimeric co-stimulation receptor target, a synNotch receptor target), and optionally a linker.

Abstract: The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Abstract: The disclosure describes amphiphilic ligand conjugates comprising a chimeric antigen receptor (CAR) ligand, a lipid (diacyl lipid), a linker (hydrophilic polymers, hydrophilic amino acids, polysaccharides), compositions and methods of using the constructs are claimed, for example, to stimulate proliferation of CAR expressing cells.

Abstract: Compositions and methods are described for inducing an immune response against an immunogen in humans. The induced immune response is obtained by administering a heterologous prime-boost combination of an in vitro transcribed (IVT) self-replicating RNA (repRNA) and an adenovirus vector. The compositions and methods can be used to provide a protective immunity against a disease, such as a viral infection or a cancer, in humans.

Abstract: The present disclosure provides a method of treating cancer with a priming dose of combination immunotherapy comprising IL-2 (e.g., extended-PK IL-2), an immune checkpoint inhibitor, a tumor targeting antibody or integrin-binding polypeptide, and optional cancer vaccine, administered prior to maintenance doses of immune checkpoint inhibitor therapy. The methods of the disclosure can be used to treat a broad range of cancer types.

Abstract: The disclosure provides methods for an in vitro evolution technique to identify and characterize mutations in the non-structural genes of an alphavirus replicon that increase the strength and persistence of expression of the replicon genome. Also provided herein are in vivo methods for administering to an animal model a mutated alphavirus replicon that codes for a gene of experimental or therapeutic interest in the subgenome of the alphavirus replicon. The mutations identified herein improve the therapeutic potential of self-replicating RNA, which may have implications for cancer immunotherapy and beyond, e.g., for vaccination or gene therapy.

Abstract: Disclosed herein are lipid nanoparticles having a specific composition, compositions including such lipid nanoparticles, and methods of treatment using such lipid nanoparticles and compositions.

Abstract: The present disclosure relates to reagents (antigenic and/or immunogenic reagents) and kits that are useful in a variety of in vitro, in vivo, and ex vivo methods including, e.g., methods for inducing an immune response, or for generating an antibody, in a subject. The reagents described herein can be used in the treatment or prevention of HIV-1 infections. In addition, the disclosure provides methods and compositions useful for designing (or identifying) an agent that binds to an membrane proximal external region (MPER) of an HIV-1 gp160 polypeptide or an agent that inhibits the fusion of an HIV-1 particle to a cell.

Abstract: The present disclosure provides particles with a polymeric core containing a pharmaceutically active agent; and an antibody fragment conjugated to the surface of the particle, wherein the antibody fragment targets an endogenous immune cell subset (e.g., an endogenous T-cell or a myeloid-derived suppressor cell). The present invention provides methods for forming and methods for using the particles. The particles described herein may be useful in treating and/or preventing proliferative disease, inflammatory disease, or neoplastic disorders (e.g., cancer, autoimmune diseases). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a particle described herein.

Abstract: Non-liposome, non-micelle particles formed of a lipid, an additional adjuvant such as a TLR4 agonist, a sterol, and a saponin are provided. The particles are porous, cage-like nanoparticles, also referred to as nanocages, and are typically between about 30 nm and about 60 nm. In some embodiments, the nanocages include or are administered in combination with an antigen. The particles can increase immune responses and are particularly useful as adjuvants in vaccine applications and related methods of treatment. Preferred lipids, additional adjuvants including TLR4 agonists, sterols, and saponins, methods of making the nanocages, and method of using them are also provided.

Abstract: The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.