Virginia Commonwealth University

Celestra Life Science LLC

Teclison Limited

Chugai Seiyaku Kabushiki Kaisha

F. Hoffmann-la Roche Ag

Ruey-Min Lee

Peck-sun Lin

Allen J Lee

Jason J Lee

David M Lu

Toshihiko Ohtomo

Anton Belousov

Gong Chen

Yasuo Sugitani

Takayoshi Tanaka

Ya-Chi Chen

Oscar Puig

Bernhard Reis

Disclosed herein are methods and compositions for enhancing an immune response to a solid tumor in a subject. In some embodiments, a method comprises: (a) administering to the subject a hypoxia-activated bioreductive agent (HABA); (b) inducing hypoxia by (i) administering a hypoxia-inducing agent to the subject or (ii) embolizing one or more blood vessels supplying the solid tumor; and (c) administering an immune checkpoint inhibitor prior to, simultaneously with, or subsequent to step (b) in an amount effective to enhance an immune response to the solid tumor, as compared to an immune response in the absence of the immune checkpoint inhibitor. Kits for use in the disclosed methods are also provided.

Compositions and methods for immune-mediated cancer therapy

A method is provided for determining the efficacy of GPC3-targeting drug therapy for cancer in a patient before the start of GPC3-targeting drug therapy or for determining the continuation of GPC3-targeting drug therapy for a patient treated with GPC3-targeting therapy. The method includes determining the number of an immunocyte or an expression level of a molecule expressed on the immunocyte in a biological sample isolated from the patient before the start of GPC3-targeting drug therapy and/or the patient treated with the GPC3-targeting drug therapy, wherein when the number of the immunocyte or the expression level of the molecule expressed on the immunocyte is a predetermined value, the efficacy of the GPC3-targeting drug therapy is determined or the continuation of the GPC3-targeting drug therapy is determined. GPC3-targeting drugs and drug preparations for use according to the disclosed methods are also provided.

GPC3-targeting drug which is administered to patient responsive to GPC3-targeting drug therapy

The methods, compositions, and kits of the invention are related to the discovery that lestaurtinib reduces levels and pathway activity of an SPOP substrate. Accordingly, described herein are methods and compositions for the use of lestaurtinib in downregulating one or more SPOP substrates or signaling pathway activities thereof in a subject in need thereof.

Rationale-based design of a targeted therapy for cancer

Methods and compositions for enhancing the ability of hypoxia-activated bioreductive agents to kill tumor cells within solid tumors are provided. Local regions of hypoxia are created within a tumor, or within a region containing a tumor, resulting in enhanced activation of hypoxia-activated bioreductive agents (e.g. tirapazamine) within the local region. The activated hypoxia-activated bioreductive agents kill tumor cells in the hypoxic region by to catalyzing DNA stand breakage within the tumor cells. Because the activity is localized, side effects that typically occur as a result of systemic administration of bioreductive agents are reduced.

Induction of tumor hypoxia for cancer therapy

Methods and compositions for enhancing the ability of hypoxia-activated bioreductive agents to kill tumor cells within solid tumors are provided. Local regions of hypoxia are created within a tumor, or within a region containing a tumor, resulting in enhanced activation of hypoxia-activated bioreductive agents (e.g. tirapazamine) within the local region. The activated hypoxia-activated bioreductive agents kill tumor cells in the hypoxic region by catalyzing DNA stand breakage within the tumor cells. Because the activity is localized, side effects that typically occur as a result of systemic administration of bioreductive agents are reduced.

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Short Hills, NJ, United States of America

Ruey-Min Lee