Abstract: Disclosed is a compound of the formula (I) or (II): wherein a f are as described herein. The compounds are useful in the activation of Type II NKT cells and in treating cancer.

Abstract: Disclosed is a method of purifying extracellular vesicles in a sample comprising extracellular vesicles and molecules that are not bound to the extracellular vesicles. The method includes (a) providing a mixed mode resin composition containing a first resin having pores with a pore size that traps unbound molecules by at least by a size exclusion mechanism, and a second resin containing at least one affinity ligand; (b) contacting the sample with the mixed mode resin composition to trap at least a portion of the unbound molecules; and (c) separating the sample from the mixed mode resin composition and obtaining a sample containing extracellular vesicles at a higher concentration than prior to step (b). Further disclosed is a method of labeling an extracellular vesicle with a fluorophore that labels proteins which includes the use of a mixed mode resin composition.

Abstract: Immunogenic compositions that include SARS-CoV-2 spike (S) protein, S1 protein, or S2 protein, and an adjuvant, such as alum, or a combination of CpG oligodeoxynucleotide, Poly I:C, and IL-15, and nanoparticle compositions that include SARS-CoV-2 S protein, S1 protein, or S2 protein, and CpG oligonucleotide, poly(I:C), and IL-15, are provided. Also provided are methods of using such compositions, for example a prime intramuscular administration followed by one or more intranasal boosters that include the disclosed nanoparticles, to generate an immune response to SARS-CoV-2 in a subject, for example respiratory mucosal immunity, for example to prevent SARS-CoV-2 infection or transmission to other subjects.

Abstract: A molecular nanotag is disclosed that includes a core nanoparticle with a diameter of less than about 100 nm, with an optional shell surrounding the core, and an armor bound to the surface of the core nanoparticle, or if present, to the surface of the shell. The molecular nanotag also includes a functionalized end with a fixed number of binding sites that can selectively bind to a molecular targeting ligand. Any one of, or any combination of, the core, the shell and the armor contribute to fluorescence, light scattering and/or ligand binding properties of the molecular tag that are detectable by microscopy or in a devices that measures intensity or power of fluorescence and light scattering.

Abstract: Recombinant adenoviruses expressing the extracellular (EC) and transmembrane (TM) domains of human HER2 (HER2ECTM) are described. The recombinant adenoviruses express a chimeric fiber protein having the adenovirus type 35 (Ad5) shaft and knob domains, which facilitates transduction of human dendritic cells by the recombinant HER2ECTM expressing adenovirus. Compositions that include dendritic cells transduced by the recombinant adenovirus and their use for treating HER-positive tumors is described.

Abstract: Flow cytometry of extracellular vesicle (EV) samples produces counts associated with channels defined by combinations of capture agents and detection agents, typically capture antibodies and detection antibodies having associated markers such as fluorophores. Sample groupings are obtained by processing channel counts using principal component analysis or other techniques. Identification of a particular sample grouping permits selection of associated channels for detection of samples exhibiting characteristics of the particular sample grouping.

Abstract: Disclosed is a compound of the formula (I) or (II): wherein a f are as described herein. The compounds are useful in the activation of Type II NKT cells and in treating cancer.

Abstract: Apparatus include an illumination source configured to produce and direct a multi-wavelength illumination beam to a microfluidic target that can include nanotags, a detector configured to receive a multi-wavelength detection beam from the microfluidic target and to produce a detection signal, wherein the multi-wavelength detection beam comprises light that is elastically side-scattered by an interaction between the multi-wavelength illumination beam and the nanotags in the microfluidic target, and a processor configured to receive the detection signal and to determine the presence of the nanotags in the microfluidic target by comparing multiple wavelength side-scatter intensity characteristics of the detection signal with predetermined multi-wavelength elastic side-scatter intensity profiles of one or more nanotag types.

Abstract: Disclosed is a method of purifying extracellular vesicles in a sample comprising extracellular vesicles and molecules that are not bound to the extracellular vesicles. The method includes (a) providing a mixed mode resin composition containing a first resin having pores with a pore size that traps unbound molecules by at least by a size exclusion mechanism, and a second resin containing at least one affinity ligand; (b) contacting the sample with the mixed mode resin composition to trap at least a portion of the unbound molecules; and (c) separating the sample from the mixed mode resin composition and obtaining a sample containing extracellular vesicles at a higher concentration than prior to step (b). Further disclosed is a method of labeling an extracellular vesicle with a fluorophore that labels proteins which includes the use of a mixed mode resin composition.

Abstract: Apparatus include an illumination source configured to produce and direct a multi-wavelength illumination beam to a microfluidic target that can include nanotags, a detector configured to receive a multi-wavelength detection beam from the microfluidic target and to produce a detection signal, wherein the multi-wavelength detection beam comprises light that is elastically side-scattered by an interaction between the multi-wavelength illumination beam and the nanotags in the microfluidic target, and a processor configured to receive the detection signal and to determine the presence of the nanotags in the microfluidic target by comparing multiple wavelength side-scatter intensity characteristics of the detection signal with predetermined multi-wavelength elastic side-scatter intensity profiles of one or more nanotag types.

Abstract: A molecular nanotag is disclosed that includes a core nanoparticle with a diameter of less than about 100 nm, with an optional shell surrounding the core, and an armor bound to the surface of the core nanoparticle, or if present, to the surface of the shell. The molecular nanotag also includes a functionalized end with a fixed number of binding sites that can selectively bind to a molecular targeting ligand. Any one of, or any combination of, the core, the shell and the armor contribute to fluorescence, light scattering and/or ligand binding properties of the molecular tag that are detectable by microscopy or in a devices that measures intensity or power of fluorescence and light scattering.

Abstract: Immunogenic T cell receptor ? alternate reading frame protein (TARP) peptide compositions that include multiple epitopes of the TARP protein are described. The disclosed compositions can be used for the treatment of TARP-expressing cancers, such as prostate cancer, breast cancer and mesothelioma. In some embodiments, the TARP peptide compositions disclosed herein include sets of overlapping TARP peptides that each have a length of about 15 to about 25 amino acids, and comprise about 5 to about 15 amino acids that are identical to at least another overlapping peptide in the set. In particular examples, the combination of the overlapping TARP peptides in the set encompasses the complete amino acid sequence of human TARP. The multi-epitope peptide compositions described herein include both CD4 and CD8 epitopes, a feature that is important for eliciting CD4+ T cell and CD8+ T cell, as well as humoral, immune responses.

Abstract: Recombinant adenoviruses expressing the extracellular (EC) and transmembrane (TM) domains of human HER2 (HER2ECTM) are described. The recombinant adenoviruses express a chimeric fiber protein having the adenovirus type 35 (Ad5) shaft and knob domains, which facilitates transduction of human dendritic cells by the recombinant HER2ECTM expressing adenovirus. Compositions that include dendritic cells transduced by the recombinant adenovirus and their use for treating HER-positive tumors is described.

Abstract: The present invention is directed to compositions comprising an immune checkpoint inhibitor or a T cell stimulator or a combination thereof, and a live attenuated recombinant Listeria strain comprising a fusion polypeptide comprising a truncated Listeriolysin O protein, a truncated ActA protein, or a PEST amino acid sequence fused to a tumor-associated antigen. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor or a cancer, comprising the step of administering the same.

Abstract: The present invention provides immunostimulatory combinations of TLR ligands and therapeutic and/or prophylactic methods that include administering an immunostimulatory combination to a subject. In general, the immunostimulatory combinations described herein can provide an increased immune response compared to other immunostimulatory combinations and/or compositions.

Abstract: The present invention is directed to methods for increasing T-cell effector cell to regulatory T cell ratio. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor, comprising the step of administering to a subject a recombinant Listeria strain, comprising a fusion peptide that comprises an LLO fragment and tumor-associated antigen.

Abstract: ?-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of ?-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising ?-mannosylceramide, as well as methods of treatment of tumors are also provided.

Abstract: Immunogenic T cell receptor ? alternate reading frame protein (TARP) peptide compositions that include multiple epitopes of the TARP protein are described. The disclosed compositions can be used for the treatment of TARP-expressing cancers, such as prostate cancer, breast cancer and mesothelioma. In some embodiments, the TARP peptide compositions disclosed herein include sets of overlapping TARP peptides that each have a length of about 15 to about 25 amino acids, and comprise about 5 to about 15 amino acids that are identical to at least another overlapping peptide in the set. In particular examples, the combination of the overlapping TARP peptides in the set encompasses the complete amino acid sequence of human TARP. The multi-epitope peptide compositions described herein include both CD4 and CD8 epitopes, a feature that is important for eliciting CD4+ T cell and CD8+ T cell, as well as humoral, immune responses.

Abstract: The present invention provides methods for lowering a viral load of a virus resistant to an antiviral drug by inducing cytotoxic T lymphocytes (CTL) to recognize a predetermined mutated epitope within a viral protein of the drug-resistant virus. CTLs are induced by immunizing a host with a peptide comprising the predetermined mutation. The immunostimulating peptide may be further improved by epitope-enhancement for inducing specific CTLs. The antiviral protection against drug-resistant virus shown by compositions of the present invention and mediated by human HLA-restricted CTL has not been previously achieved.

Abstract: The present invention provides immunostimulatory combinations of TLR ligands and therapeutic and/or prophylactic methods that include administering an immunostimulatory combination to a subject. In general, the immunostimulatory combinations described herein can provide an increased immune response compared to other immunostimulatory combinations and/or compositions.