Johns Hopkins University

Chien-Fu Hung

Tzyy-Choou Wu

T C Wu

Chih-Ping Mao

Ralph Hruban

Elizabeth A Jaffee

Jie Xiao

Shih-Chin Wang

Brandon Krishna Lam

Tzvv-Choou Wu

Tzyy Choou Wu

Brandon Lam

This document relates to methods and materials for assessing and/or treating mammals (e.g., humans) having, or suspected of having, cancer. For example, methods and materials for identifying a mammal as having cancer are provided. For example, microfluidic devices that can be used to detect one or more target polypeptides (e.g., cancer-specific polypeptides) in a fluid sample obtained from a mammal (e.g., a mammal suspected of having cancer) are provided.

Methods and materials for treating cancer

Described are chips for detecting a target in a sample including a microfluidic flow chamber comprising one or more flow channels having a capture surface and at least one micromixer. Described are methods of using this chip wherein targets are identified by total internal reflection fluorescence (TIRF).

Non-invasive cancer detection and analysis by single-molecule imaging

The present invention provides a novel fusion protein of Flt3L and albumin and its use to increase the Flt3L half-life in vivo and to deliver Flt3L to immune cells in a subject to enhance alternative dendritic cell populations. Use of the fusion protein in combination with other chemotherapeutic, radiotherapeutic and immunotherapeutic methods are also provided.

Compositions comprising albumin-FMS-like tyrosine kinase 3 ligand fusion proteins and uses thereof

The disclosure features compounds comprising an antigen portion, a soluble Major Histocompatibility Complex (MHC) molecule portion (e.g., all or an antigen-binding portion of a soluble MHC class I molecule), and a dynamic anchor portion (e.g., an agent, such as Annexin V, that binds to phosphatidylserine). The featured compounds are useful for a variety of therapeutic applications, including, e.g., enhancing a T cell response to an antigen of interest or enhancing a T cell-driven immune response by a subject to an antigen of interest (e.g., a cancer antigen or a microbial antigen).

Compositions and methods for enhancing an immune response

Described herein are methods comprising administering to a mammalian subject an effective amount of an annexin chimeric fusion protein, wherein the annexin chimeric fusion protein comprises at least one immunogenic antigen, thereby enhancing the antigen specific immune response relative to administration of the immunogenic antigen alone. Methods and kits for treating or preventing recurrence of hyper proliferating diseases, e.g., cancer, are described. A method may comprise priming a mammal by administering to the mammal an effective amount of a chemotherapeutic agent and boosting the mammal by administering to the mammal an effective amount of an annexin chimeric fusion.

Methods for enhancing antigen-specific immune responses

Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

Mesothelin vaccines and model systems

Described herein are methods comprising administering to a mammalian subject an effective amount of an annexin chimeric fusion protein, wherein the annexin chimeric fusion protein comprises at least one immunogenic antigen, thereby enhancing the antigen specific immune response relative to administration of the immunogenic antige alone. Methods and kits for treating or preventing recurrence of hyper proliferating diseases, e.g., cancer, are described. A method may comprise priming a mammal by administering to the mammal an effective amount of a chemotherapeutic agent and boosting the mammal by administering to the mammal an effective amount of an annexin chimeric fusion.

The present invention provides an immunoconjugate having the formula:T-c-E-c-Fcor T-c-Fc-c-E;wherein, T is a single chain variable portion fragment of a monoclonal antibody (scFv) directed to a target protein, polypeptide, or fragment thereof, which is highly expressed on cancer cells; E is two or more foreign immunogenic CD8T cell antigenic epitopes; c is a peptide or polypeptide fragment thereof, capable of being cleaved by a specific protease; and Fc is two or more Fc portions of an IgG antibody. Nucleic acid sequences encoding the same and vectors containing said nucleic acid sequences are also provided. Methods of making the immunoconjugate, along with methods of making target cells susceptible to CTL mediated cell killing, and methods for treatment of cancers are also provided.

Compositions and methods for rendering tumor cells susceptible to CD8+ T cell-mediated killing

Nucleic acids encoding a chimeric or fusion polypeptide which polypeptide comprises a first domain comprising a translocation polypeptide; and a second domain comprising at least one antigenic peptide are disclosed. The preferred translocation polypeptide is a bacterial toxin translocation polypeptide, such as domain II ofexotoxin A (ETA(dII)). Such nucleic acids, expression vectors thereof, and cells expressing these vectors are used as vaccine compositions in a method for enhancing an antigen specific immune response, a method of increasing the numbers of CD8CTLs specific for a selected desired antigen in a subject, or a method of inhibiting the growth of a tumor in a subject.

Superior molecular vaccine linking the translocation domain of a bacterial toxin to an antigen

Novel nucleic acid vectors comprising sequences encoding (a) an antigen, (b) a signal peptide, and (c) a heat shock protein, are disclosed, as are methods for using such vectors to induce antigen-specific immune responses and to treat tumors.

Anti-cancer DNA vaccine employing plasmids encoding signal sequence, mutant oncoprotein antigen, and heat shock protein

The present invention provides an immunoconjugate having the formula: T-c-E-c-Fcor T-c-Fc-c-E; wherein, T is a single chain variable portion fragment of a monoclonal antibody (scFv) directed to a target protein, polypeptide, or fragment thereof, which is highly expressed on cancer cells; E is two or more foreign immunogenic CD8T cell antigenic epitopes; c is a peptide or polypeptide fragment thereof, capable of being cleaved by a specific protease; and Fc is two or more Fc portions of an IgG antibody. Nucleic acid sequences encoding the same and vectors containing said nucleic acid sequences are also provided. Methods of making the immunoconjugate, along with methods of making target cells susceptible to CTL mediated cell killing, and methods for treatment of cancers are also provided.

Methods for treating or preventing hyperproliferating diseases, e.g., cancer, are described. A method may comprise administering to a subject in need thereof a therapeutically effective amount of a nucleic acid encoding an MHC class I and/or II activator and optionally a nucleic acid encoding an antigen.

DNA vaccine enhancement with MHC class II activators

An immunotherapeutic strategy is disclosed that combines antigen-encoding DNA vaccine compositions combined with siRNA directed to pro-apoptotic genes, primarily Bak and Bax, the products of which are known to lead to apoptotic death. Gene gun delivery (particle bombardment) of siRNA specific for Bak and/or Bax to antigen-expressing DCs prolongs the lives of such DCs and lead to enhanced generation of antigen-specific CD8+ T cell-mediated immune responses in vivo. Similarly, antigen-loaded DC's transfected with siRNA targeting Bak and/or Bax serve as improved immunogens and tumor immunotherapeutic agents.

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Timonium, MD, United States of America

Chien-Fu Hung