The Wistar Institute

University of Pennsylvania

Meenhard Herlyn

Hilary Koprowski

Ulrich Rodeck

Zenon Steplewski

Dorothee Herlyn

Frank J Rauscher, Iii

Jennifer Morris

Xiaowei Xu

Jan Thurin

Douglas Dong Fang

Rajasekharan Somasundaram

Rajasckharan Somasundaram

Jiri Kalabis

Mark Nesbit

Alonzo Ross

Kapaettu Satyamoorthy

Hong Yu

Gao Zhang

Dario Carlo Altieri

Qin Liu

Compositions and methods for treating melanoma are provided. Compositions include BRAF-based peptides, alone or admixed with T helper peptides. Other compositions include nucleic acid sequences encoding the BRAF-based peptides, alone or admixed with nucleic acid sequences T helper peptides. Dendritic cells pretreated with the BRAF-based peptides, alone or admixed with T helper peptides, are also provided. These compositions are useful to treat melanoma, optionally co-administered with antibodies to checkpoint inhibitors or molecules that mimic the action of such antibodies.

Methods and compositions for treating melanoma

Isolated human multipotent adult stem cell and isolated populations of cells that include human multipotent adult stem cells are disclosed. Human hair-follicle derived multipotent adult stem cells and methods of preparing isolated populations of cells that include human multipotent adult stem cells are disclosed. Isolated human hair-follicle derived multipotent adult stem cell that can differentiate in culture into a neuronal cell, a glial cell, a melanocyte cell, a muscle cell, an osteocyte, a chondrocyte, and a lymphocyte. Isolated human hair-follicle derived multipotent adult stem cell that can grow in cell culture in spheres are disclosed. Human pancreas derived multipotent adult stem cells, human liver derived multipotent adult stem cells, human kidney derived multipotent adult stem cells, human heart derived multipotent adult stem cells, human neural derived multipotent adult stem cells and methods of preparing isolated populations of cells that include such human multipotent adult stem cells are disclosed. Method of treating an individual who has diabetes, cardiac muscle damage, muscle damage and disease, neurodegenerative disease or nerve damage or injury, bone loss, damage and/or disease, cartilage loss, damage and/or disease, hair loss and immune disorders, are disclosed.

Methods for preparation of human hair-follicle derived multipotent adult stem cells

A three-dimensional reconstruct model containing solid layers of collagen and fibroblasts closely mimic the condition of patients in vivo, preserving in vivo phenotypic and functional characteristics of the cells. Reconstructs can be used to detect cellular migration, including active migration of cytotoxic T lymphocytes towards tumor cells, which can be measured by detecting tumor cell lysis. Reconstructs also can be used to identify factors that influence migration of cells, including chemokines that influence migration of cytotoxic T lymphocytes, as well as to identify tumor antigens.

Methods and compositions for monitoring cell migration and identifying clinically relevant cytotoxic T lymphocyte activity

An organotypic culture comprises an artificial stroma overlayed with epithelial cells isolated from a human colon or intestine. The stroma comprises a mixture of collagen and human fibroblasts isolated from a human colon or intestine. The culture contains a factor that binds the IGF-1 receptor, a factor that binds the EGF receptor, and a factor that binds the LIF receptor. These factors may be added exogenously to the culture via medium or may be expressed by various recombinantly engineered cell types in the culture. The organotypic culture can result in growth that is in situ-like or emphasizes other physiological or morphological states, depending on the balance of factors in the growth media. The organotypic culture may be used in methods for screening of therapeutic, carcinogenic, or growth enhancement factors, or for treating intestinal injuries by applying to the site of an injury the intact culture or the components thereof.

Organotypic intestinal culture and methods of use thereof

A method for repairing defects and inducing vascularization in mammalian tissue, preferably skin, involves administering to the tissue a recombinant replication defective virus, preferably adenovirus, carrying a selected growth factor gene, preferably VEGF or PDGF, under operative control of regulatory sequences which direct the expression of the growth factor(s). Also provided is a method for infecting a tissue to be transplanted with such recombinant adenoviruses prior to transplantation and, as a composition, an infected culture of human tissue to be transplanted which is infused with a selected growth factor prior to transplantation. Screening methods for the treatment of angiogenic disorders, e.g., hemangiomas and cancers, also employ an animal model on which is engrafted a full thickness human tissue infused with a growth factor.

Methods for inducing localized vascular development and enhancing the repair of a wound in the mammamian dermis

The present invention provides three unique monoclonal antibodies directed against a portion of the Wilms' tumor antigen, and methods of use therefor in detecting, monitoring and diagnosing malignancies characterized by over-expression or inappropriate expression of the WT 1 protein.

WT1 monoclonal antibodies and methods of use therefor

Three unique monoclonal antibodies, each having an epitope located in amino acids 1-181 of the WT1 tumor protein, and the hybridomas which secrete them have been constructed. These monoclonal antibodies are useful in the detection, monitoring, and diagnosis of malignancies characterized by inappropriate expression of the WT1 protein.

WT1 monoclonal antibodies

Monoclonal antibody 425 having properties particularly beneficial for anti-tumor therapy has been raised. MAb 425 antibody binds to EGF-receptors and inhibits their bioactivities. The amount of binding of the antibody to cancer cells can be increased by treatment of the cells with lymphokine preparations. Radiolabeled MAb 425 is used for treatment of EGF receptor-expressing gliomas.

Method of treating human EGF receptor-expressing gliomas using

The present invention is directed to monoclonal antibodies, and hybridomas which produce them, which are reactive with ganglioside antigens GD2 and GD3 and are essentially non-reactive with other ganglioside antigens. The invention further relates to methods of using these antibodies.

Monoclonal antibodies against melanoma-associated antigens and hybrid

It has been determined that nerve growth factor binds to a cell surface protein of human neural crest origin having a molecular weight of about 75,000 daltons. New monoclonal antibodies specifically imunoprecipitate these receptor molecules, and also inhibit binding of the hormone to the receptor. These monoclonal antibodies show significantly higher reactivity with primary and metastatic melanoma cell lines than with melanocytes. The antibodies are used in a diagnostic method for histochemical detection of human neural crest disease.

Diagnostic method for detection of neural crest disease

An assay for determining the Lewis blood group of a patient consists of testing a body sample for the presence of Lewis.sup.a and Lewis.sup.b antigens. Monoclonal antibodies specific for either of these antigens are employed which do not cross-react with other related antigens, such as the H blood antigen. Body samples which may be tested include: saliva, serum, urine, and paraffin-embedded tissue samples. Hybridoma cell lines and the antibody compositions they produce specific for these antigens are provided for use in the assay.

Lewis blood group phenotype assay

Colorectal carcinoma is detected by testing body fluids for the colorectal carcinoma monosialoganglioside identified by monoclonal antibodies produced by fused cell hybrid ATCC HB 8059.

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Wynnewood, PA, United States of America

Meenhard Herlyn