Mayo Foundation for Medical Education and Research

The United States of America, as Represented by the Secretary, Department of Health and Human Services

The Translational Genomics Research Institute

University of Illinois

George Vasmatzis

Farhad Kosari

Eric W Klee

Ira H Pastan

Byungkook Lee

John C Cheville

Lori S Tillmans

Ulrich Brinkmann

Michael Richard Barrett

George G Klee

David Craig

Mitesh J Borad

John Carpten

Keith Stewart

Sara Byron

Cemile D Savci-Heijink

Jan Marie A Willard

Andrew L Feldman

Jessica Aldrich

Alan Bryce

Satoshi Nagata

Rashid Bashir

Anurup Ganguli

Curt Douglas Wolfgang

Masanori Onda

David I Smith

Robert Kreitman

James Vincent

Magnus Essand

Ahmet Dogan

Mark Law

Cemile Dilara Savci Heijink

Jan-Marie Willard Munz

Yasuo Tsutsumi

Panagiotis Z Anastasiadis

Marie-Christine Aubry

Cristiane M Ida

Sarah H Johnson

Rhett P Ketterling

Ryan A Knudson

Kathryn E Pearce

Julie C Porcher

Various embodiments provide compositions and methods for detecting cancers containing an NRG1 fusion event and treating a patient with a therapeutic agent that is targeted to the NRG1 fusion. Exemplary compositions for treating cancers containing the NRG1 fusion may comprise therapeutic agents inhibiting Epidermal Growth Factor Receptor and/or ERBB2 such as cetuximab, panitumumab, Sym004, MM-151, mAb 806, mAb 528, MEHD794A, gefitinib, erlotinib, lapatinib, afatinib, PD153035, AG1478, trastuzumab, and pertuzumab. In some embodiments, the therapeutic agent may be a combination of trastuzumab, and pertuzumab.

Targeted therapies for cancer

Provided are methods and related devices for preparing a cell and tissue culture, including a hanging drop culture. Microwells are specially loaded with cell mixtures using a removable reservoir and forcing cells into the underlying microwells. The removable reservoir is removed and the cells partitioned into the individual microwells and covered by an immiscible layer of fluid. The microwells and immiscible layer is inverted and the cells in the microwells cultured. The microwells may have shape-controlling elements to control the three-dimensional shape of the culture.

Microchip high density hanging drop three-dimension culture platform

This document provides methods and materials related to assessing prostate cancer in mammals. For example, this document provides nucleic acids and polypeptides that can be analyzed to determine whether a male mammal having prostate cancer is susceptible to a good or poor outcome.

Predicting cancer outcome

This document provides methods and materials involved in identifying mammals having lung adenocarcinoma characterized by neuroendocrine differentiation as well as methods and materials involved in treating mammals having lung adenocarcinoma characterized by neuroendocrine differentiation. For example, methods and materials for using ASCL1 and RET expression levels to identify lung cancer patients having lung adenocarcinoma characterized by neuroendocrine differentiation are provided.

Methods and materials for identifying and treating mammals having lung adenocarcinoma characterized by neuroendocrine differentiation

This document provides methods and materials involved in detecting translocations of TBL1XR1 and TP63 nucleic acid. For example, methods and materials for detecting TBL1XR1 and TP63 gene rearrangements (e.g., translocations) associated with cancer (e.g., T-cell lymphomas) as well as methods and materials for detecting cancers (e.g., T-cell lymphomas) with a dominant negative TP63 phenotype are provided.

TBL1XR1 and TP63 translocations

This document relates to methods and materials involved in identifying, assessing, and monitoring prostate cancer in male mammals. For example, this document provides arrays for detecting polypeptides or nucleic acids that can be used to identify prostate cancer in male mammals. In addition, methods and materials for assessing and monitoring prostate cancer in mammals are provided herein.

Extracellular and membrane-associated prostate cancer markers

This document relates to the activity of interferon regulatory factor 4 (IRF4) in T-cell lymphomas. For example, methods and materials involved in reducing the expression of an IRF4 polypeptide in T-cell lymphoma cells and identifying agents having the ability to reduce expression of an IRF4 polypeptide in T-cell lymphoma cells are provided. This document also relates to reducing DUSP22 or FLJ43663 polypeptide activity in T-cell lymphomas. For example, methods and materials involved in reducing the expression of DUSP22 polypeptides and/or FLJ43663 polypeptides in T-cell lymphoma cells and identifying agents having the ability to reduce expression of DUSP22 polypeptides and/or FLJ43663 polypeptides in T-cell lymphoma cells are provided.

Reducing IRF4, DUSP22, or FLJ43663 polypeptide expression

The invention provides recombinant immunotoxins that have been modified from a parental immunotoxin to lower liver toxicity. The immunotoxins are created by specifically mutating charged residues in the framework regions of the heavy chain, the light chain, or both, of the antibody portion or antigen-binding fragment thereof of the parental immunotoxin to reduce the pI of the antibody or fragment. In preferred forms, the antibody portion of the parental is an anti-Tac, anti-mesothelin, or anti-LewisY antigen antibody or antigen-binding fragment, and in particularly preferred forms the antibody portion is an M16 dsFv, a St6 dsFv or a Mt9 dsFv, or a sequence that has at least 90% sequence identity to one of these molecules but retain the particular mutations that lower pI without affecting antibody activity. The invention further provides nucleic acids encoding the recombinant immunotoxins of the invention, expression cassettes comprising the nucleic acids, and host cells comprising the expression cassettes. The invention also provides a method for killing a cell comprising an antigen on the surface of the cell, the method comprising contacting the cell with a recombinant immunotoxin of the invention that has an antibody or antigen-binding fragment thereof that binds specifically to the antigen on the surface of the cell, and uses of immunotoxins of the invention for the manufacture of medicaments.

Reduction of the nonspecific animal toxicity of immunotoxins by mutating the framework regions of the Fv to lower the isoelectric point

PAGE-4 is a gene preferentially expressed in normal male and female reproductive tissues, prostate, testis, fallopian tube, uterus and placenta, as well as in prostate cancer, testicular cancer and uterine cancer. This expression pattern makes it a target for diagnosis and for vaccine based therapy of neoplasms of prostate, testis and uterus. The invention provides immunogenic compositions comprising PAGE-4 protein or immunogenic peptides thereof, methods of inhibiting the growth of malignant cells expressing PAGE-4, and methods of inducing an enhanced immune response to PAGE-4-expressing cancers.

Page-4, an x-linked gage-like gene expressed in normal and neoplastic prostate, testis and uterus, and uses therefor

This invention provides nucleic acids containing sequences from a TCR&#x3b3; transcript from prostate epithelial cells and many breast cancer cells and a T-cell receptor gamma Alternate Reading frame Protein ('TARP') expressed from the translation of those sequences. Vaccines made from TARP are useful in raising immune responses to cells in which the protein is expressed, including prostate cancer cells and cells of many breast cancers. The invention also provides methods for diagnosing the presence of prostate cancer and TARP-expressing breast cancers, as well as methods of administering TARP and nucleic acids encoding TARP to subjects.

T-cell receptor&#x3b3; alternate reading frame protein, (TARP) and uses thereof

Growing community of inventors

Byron, MN, United States of America

George Vasmatzis