University of Virginia Patent Foundation

Craig L Slingluff, Jr

Donald F Hunt

Victor H Engelhard

Jeffrey Shabanowitz

David Kittlesen

Andrea L Cox

William H Guilford

Jonathan Skipper

Ronald C Hendrikson

Joshua M Judge

Victor M Engelhard

Kevin T Hogan

Ileana S Mauldin

Toll-like receptor (TLR) agonists can induce chemokine production. We find that TLR2 and TLR6 are widely expressed on human melanoma cells, and that TLR2/6 agonists (MALP-2 or FSL-1) synergize with interferon-gamma (IFN&#x3b3;) to induce production of CXCL10 from melanoma cells. Furthermore, melanoma cells and immune cells freshly isolated from surgical specimens also respond to TLR2/6 agonists +IFN&#x3b3; by upregulating CXCL10 production, compared to treatment with either agent alone. It is also disclosed herein that these compounds are useful in inducing CLXL10 in other types of cancer. Collectively, these data identify a novel synergy of TLR2/6 agonists +IFN&#x3b3; for inducing CXCL10 production directly from melanoma cells, raising the possibility that intratumoral administration of these agents may improve immune signatures in melanoma and have value in combination with other immune therapies, by supporting T-cell migration into melanoma metastases.

Compositions and methods for treating melanoma

An insertion tongue of the retractor device may be pushed into the subject through the trocar incision, along one side of the organ. The tip of the insertion tongue pushes the impacted organ and its endoscopic recovery bag slightly away from the cavity wall. A scalpel is passed through the insertion guide with the tip of the scalpel blade in the retention guide on the back of the insertion tongue, and with the sharp side of the scalpel blade facing away from the organ and from the tongue of the retractor device. The scalpel is then passed down through the cavity wall, with its tip in the retention guide, while tension on the retractor device handle away from the organ, and gentle outward traction on the organ (and bag) permits removal of the organ (and bag) as soon as the opening is just large enough to allow it.

Device and method for safely expanding minimally invasive surgical incisions

The present invention encompasses novel peptides useful for preventing and treating cancer, particularly melanoma. Multiple sequences of interest are provided and these sequences have been incorporated into other peptides to obtain a series of peptides of about 30 amino acid residues in length wherein the properties of each combine to yield an effective cocktail for treating melanoma, which surpasses the use of single peptides as immunogens, as well as shorter peptides as immunogens.

Composition and methods for treating melanoma

The present invention is directed to a newly discovered gene family with multiple isoforms, designated TAG-1, TAG-2a, TAG-2b, TAG-2c, and TAG-3, nucleic acid sequences encoding those proteins, and antibodies generated against said proteins. The genes, proteins, and peptides described herein may be used as diagnostic indicators of the presence of cancer and/or used in therapeutics to treat cancer.

TAG-1 and TAG-2 proteins and uses thereof

Melanoma-specific, A1- and A3-restricted CTL epitopes have been identified in tyrosinase and pMel-17, respectively, and may be used in the design of vaccines.

Peptides recognized by melanoma-specific A1-, A2- and A3-restricted cytoxic lymphocytes, and uses therefor

The instant disclosure identifies and synthesizes peptide residues initially isolated from a melanoma cell line. The peptides are capable of reconstituting an epitope recognized by tumor specific CTL. Some of the sequences are homologous with proteins identified as pMEL17, tyrosinase and cofilin. The present invention provides for the treatment of melanoma patients using synthetic peptides that reconstitute epitopes for melanoma specific CTL. In another embodiment the peptides are used as vaccines for imparting immunity. Alternatively, in one embodiment the peptides may be used to bind to antigen presenting cells in a method for providing specific antigenic stimulation of CTL. The instant invention provides CTL cell lines capable of recognizing reconstituted HLA-A2.1 epitopes and their use in methods of adoptive immunotherapy. The invention additionally provides for genes encoding for peptides capable of reconstituting epitopes recognized by tumor specific CTL and their use as vaccines in the prevention and management of melanoma. A splitter is also disclosed to identify active peptides.

Peptides recognized by melanoma-specific cytotoxic lymphocytes, and uses therefor

Cysteine-depleted CTL epitopes can elicit a stronger or more specific CTL response than the native, cysteine-containing CTL epitope of a disease associated antigen.

Growing community of inventors

Charlottesville, VA, United States of America

Craig L Slingluff, Jr