National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Department of Health

The University of Birmingham

The United States of America As Represented by the Secretary of

University of Connecticut

Baylor College of Medicine

The United States of America, As Represented by the Secretary, Departmenf Health and Human Services

Jay A Berzofsky

Masaki Terabe

Mutsunori Shirai

C David Pendleton

Ira H Pastan

Stephen M Feinstone

Peter L Nara

Jeffrey D Ahlers

Lee J Helman

Samir N Khleif

Gurdyal S Besra

Ronald N Germain

Marian Elaine Major

Jessica J O'Konek

Petr Illarionov

Akihiko Kurata

Pablo Sarobe

Theresa J Goletz

Leon T Van Den Broeke

Takahiro Okazaki

Joshua Aden Welsh

Jennifer C Jones

Stephen H Leppla

Crystal L Mackall

Yi-Hsiang Huang

Louis H Miller

James L Cornette

Naveen Arora

Kurt Klimpel

Ari Rosner

Brenda D Roberson

Hidemi Takahashi

Anne Hosmalin

Hanah Margalit

SangKon Oh

Lauren V Wood

Igor Belyakov

Bernard Moss

Stewart K Richardson

Samuel Broder

Malcolm K Brenner

Thomas Alexander Waldmann

Warren Strober

Robert Yarchoan

Gene M Shearer

Amy R Howell

Mario S Clerici

Charles DeLisi

Liyanage Parakrama Perera

Brian L Kelsall

William G Telford

Toshitaka Akatsuka

Toshiyuki Taskeshita

Steven Kozlowski

C David Pendelton

Michael A Good

Lise H Pasquet

Kaddy Camara

Katherine M McKinnon

Jiahua Qian

Crystal MacKall

John C Morris

David H Margulies

Sang-Kon Oh

Aizea Morales-Kastresana

Andrew Catanzaro

Michael A Derby

Paula M Hale

Jason C Steel

James T Snyder, Ii

John L Spouge

Michael F Good

Sanjai Kumar

Qing Zhu

Kemp B Cease

Cecilia S Ouyang

Charles D Pendleton

Hajime Kawamura

Masaki R Terabe

Thomas A Waldmann

Liyange P Perera

So Matsui

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.

3-o-sulfo-galactosylceramide analogs as activators of type II NKT cells and uses thereof

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.

Purification and labeling of extracellular vesicles using a mixed mode resin composition

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. The light scattering intensity or power of the assembled structure is detectable above the specific level of the reference noise of a device detecting the light scattering intensity or power, its fluorescence intensity or power has sufficient brightness for detection above the limit of detection for the instrument, and ligand specificity is conferred by the ligand binding component. Methods of biomarker and biosignature detection using the molecular tags are also disclosed.

Molecular nanotags

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.

Compositions and methods for the treatment of HER2-expressing solid tumors

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. Methods are also disclosed that determine the presence of different nanotags responsive to a multi-wavelength detection beam based on a detected signal and predetermined multi-wavelength elastic side-scatter intensity profiles for different nanotag types.

Optical configuration methods for spectral scatter flow cytometry

Immunogenic T cell receptor &#x3b3; 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 CD4T cell and CD8T cell, as well as humoral, immune responses.

Multi-epitope TARP peptide vaccine and uses thereof

&#x3b2;-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 &#x3b1;-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising &#x3b2;-mannosylceramide, as well as methods of treatment of tumors are also provided.

Beta-mannosylceramide and stimulation of NKT cell anti-tumor immunity

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.

Vaccines and methods for prevention and treatment of drug-resistant HIV-1 and hepatitis B virus

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.

Immunostimulatory combinations of TLR ligands and methods of use

POTE has recently been identified as a tumor antigen expressed in a variety of human cancers, including colon, ovarian, breast, prostate, lung and pancreatic cancer. Described herein are immunogenic POTE polypeptides, including modified POTE polypeptides, that bind MHC class I molecules. The immunogenic POTE polypeptides are capable of inducing an immune response against POTE-expressing tumor cells. Thus, provided herein is a method of eliciting an immune response in a subject, such as a subject having a type of cancer that expresses POTE.

Immunogenic POTE peptides and methods of use

Disclosed are immunogenic peptides, related fusion proteins, nucleic acids encoding the peptides or fusion proteins, conjugates, expression vectors, host cells, and antibodies. Also, disclosed are pharmaceutical compositions, vaccines for use in the treatment or prevention of cancer, e.g., alveolar rhabodomyosarcoma, methods of stimulating a T cell to kill a tumor cell, methods of stimulating CD4and CD8T cells, and methods of treating or preventing cancer are further provided herein.

Immunogenic peptides and methods of use for treating and preventing cancer

&#x3b2;-mannosylceramide and stimulation of NKT cell anti-tumor immunity

The present invention provides compositions comprising a vector including a nucleic acid comprising a nucleotide sequence encoding a peptide having the sequence XLYQYMDDV, wherein Xis any hydrophobic amino acid. The compositions are used to induce an immune response against human immunodeficiency virus (HIV).

Compositions comprising nucleic acids encoding HIV-1 reverse transcriptase CTL epitopes

Growing community of inventors

Bethesda, MD, United States of America

Jay A Berzofsky