Johns Hopkins University

Biomed Valley Discoveries, Inc.

Shibin Zhou

Bert Vogelstein

Kenneth W Kinzler

Saurabh Saha

Ian Cheong

Martin Gilbert Pomper

Nickolas Papadopoulos

Chetan Bettegowda

Catherine Anne Foss

Leigh Zawel

KiBem Kim

Gregory J Riggins

Renyuan Bai

Verena Staedtke

Qing Wang

Michael S Hwang

Jacqueline Douglass

Emily Han-Chung Hsiue

Kibem Kim

Kenneth Kinzler

The present invention provides, inter alia, methods for treating or ameliorating an effect of a solid tumor present in a non-human animal. These methods include administering intratumorally to the non-human animal a unit dose of, preferablyNT, colony forming units (CFUs), which contains about 1×106-1×1010 CFUs suspended in a pharmaceutically acceptable carrier or solution. Methods for debulking a solid tumor present in a non-human animal, a method for microscopically precise excision of tumor cells in a non-human animal, methods for treating or ameliorating an effect of a solid tumor that has metastasized to one or more sites in a non-human animal, methods for ablating a solid tumor present in a non-human animal, unit doses of, preferablyNT, CFUs, and kits for treating or ameliorating an effect of a solid tumor present in a non-human animal are also provided.

C. novyi for the treatment of solid tumors in non-human animals

The presently disclosed subject matter provides methods and kits for treating solid tumors in a subject by using a combination of anti-CTLA-4 and/or anti-PD-1 antibodies with at least one member of the group consisting of a bacterium, bacterial product, and an immunoregulatory entity. In particular embodiments, the bacteria are toxin-depleted, anaerobic bacteria, such as-NT.

Use of bacteria, bacterial products, and other immunoregulatory entities in combination with anti-CTLA-4 and/or anti-PD-1 antibodies to treat solid tumor malignancies

This document provides methods and materials for assessing a mammal having or suspected of having cancer and/or for treating a mammal having cancer. For example, molecules including one or more antigen-binding domains (e.g., a single-chain variable fragment (scFv)) that can bind to a modified peptide (e.g., a tumor antigen), as well as method for using such molecules, are provided.

MANAbodies and methods of using

This document provides methods and materials for preventing cytokine release syndrome (CRS). For example, methods and materials for using one or more catecholamine inhibitors to prevent a mammal from developing CRS are provided.

Preventing cytokine release syndrome

The present invention provides, inter alia, methods for treating or ameliorating an effect of a solid tumor present in a human. These methods include administering intratumorally to the human a unit dose of, preferablyNT, colony forming units (CFUs), which contains about 1&#xd7;10-1&#xd7;10CFUs suspended in a pharmaceutically acceptable carrier or solution. Methods for debulking a solid tumor present in a human, methods for ablating a solid tumor present in a human, a method for microscopically precise excision of tumor cells in a human, methods for treating or ameliorating an effect of a solid tumor that has metastasized to one or more sites in a human, unit doses of, preferablyNT, CFUs, and kits for treating or ameliorating an effect of a solid tumor present in a human are also provided.

C. novyi for the treatment of solid tumors in humans

Impressive responses have been observed in patients treated with checkpoint inhibitory anti-PD-1 or anti-CTLA-4 antibodies. However, immunotherapy against poorly immunogenic cancers remains a challenge. Treatment with both anti-PD-1 and anti-CTLA-4 antibodies were unable to eradicate large, modestly immunogenic CT26 tumors or metastatic 4T1 tumors. However, co-treatment with epigenetic modulating drugs and checkpoint inhibitors markedly improved treatment outcomes, curing more than 80% of them. Functional studies revealed that the primary targets of the epigenetic modulators were myeloid-derived suppressor cells (MDSCs). A PI3K-inhibitor that reduced circulating MDSCs also cured 80% of mice with metastatic 4T1 tumors when combined with immune checkpoint inhibitors. Thus, cancers resistant to immune checkpoint blockade can be cured by eliminating MDSCs.

Suppression of myeloid derived suppressor cells and immune checkpoint blockade

for the treatment of solid tumors in humans

is an obligate anaerobe that can infect hypoxic regions within experimental tumors. We found that mice bearing large, established tumors were often cured when treated withplus a single dose of liposomal doxorubicin. The secreted factor responsible for this phenomenon was identified and, surprisingly, proved to be a member of the lipase family. The gene encoding this protein, called liposomase, has the potential to be incorporated into diverse therapeutic methods to deliver specifically a variety of chemotherapeutic agents to tumors.

Tumor-specific delivery of therapeutic agents via liposomase

The instant invention provides a method for diagnosing an infection in a subject by administering to the subject a compound suitable for imaging which binds to a thymidine kinase present in the infecting organism, and obtaining an image of the subject to determine the presence and location of the compound, wherein a localization of the compound is indicative that the subject has an infection.

Imaging infection with compounds that bind to thymidine kinase

Tumor specific delivery of therapeutic agents via liposomase

hFAST-1 is a human forkhead activin signal transducer gene. The hFAST-1 protein has the ability to bind to human Smad2 and activate an activin response element (ARE). The hFAST-1-dependent activation of ARE is dependent on endogenous Smad4 and stimulation of the TGF-&bgr; receptor. The hFAST-1 protein binds to a novel DNA motif, TGT(G/T)(T/G)ATT, which is present within the ARE. This motif is important for the activation of genes responsive to ligands of the TGF-&bgr; family. The invention includes tools for investigating the TGF-&bgr; signaling pathway and screening for compounds which modulate the action of TGF-&bgr;.

Human fast-1 protein

hFAST-1 is a human forkhead activin signal transducer gene. The hFAST-1 protein has the ability to bind to human Smad2 and activate an activin response element (ARE). The hFAST-1-dependent activation of ARE is dependent on endogenous Smad4 and stimulation of the TGF-.beta. receptor. The hFAST-1 protein binds to a novel DNA motif, TGT(G/T)(T/G)ATT, which is present within the ARE. This motif is important for the activation of genes responsive to ligands of the TGF-.beta. family. The invention includes tools for investigating the TGF-.beta. signaling pathway and screening for compounds which modulate the action of TGF-.beta..

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Owings Mills, MD, United States of America

Shibin Zhou