Combination of local and systemic immunomodulative therapies for enhanced treatment of cancer
Inventors
Eagle, Craig J. • Dees, H. Craig • Wachter, Eric A. • Singer, Jamie
Assignees
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Publication Number
US-9107887-B2
Publication Date
2015-08-18
Expiration Date
Abstract
A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.
Core Innovation
The invention relates to a method of treatment of a melanoma, or primary or metastatic liver cancer in a human. The method comprises separately administering an intralesional chemoablative pharmaceutical composition to elicit ablation of at least one melanoma or primary or metastatic liver cancerous tumor, and then administering a systemic immunomodulatory anticancer agent in a combination therapeutic regimen.
The intralesional chemoablative pharmaceutical composition comprises an intralesional chemoablative agent comprising rose bengal in an appropriate pharmaceutical composition, including an aqueous rose bengal formulation or a physiologically acceptable salt of rose bengal. The composition is administered intralesionally into the melanoma or primary or metastatic liver cancerous tumor.
The invention rationale is directed to local rapid tumor disruption by intralesional chemoablation, exposing intact antigens to elicit a bystander antitumor immune response. The systemic immunomodulatory anticancer agent is used to reduce tumor-driven immune suppression and to achieve synergy or additive effects in combination with the intralesional chemoablative treatment.
Claims Coverage
The document provides one independent claim. The inventive features are centered on two elements: intralesional chemoablative rose bengal treatment of melanoma or primary or metastatic liver tumor tissue, and subsequent systemic immunomodulatory anticancer treatment that modulates immune system down-regulation or immune system up-regulation.
Sequential intralesional chemoablation followed by systemic immune modulation
A method of treatment of a human with melanoma, or primary or metastatic liver cancer, comprising separately administering an intralesional chemoablative pharmaceutical composition to elicit ablation of at least one tumor, followed by administration of a therapeutically effective amount of a systemic immunomodulatory anticancer agent that is a systemic enhancer of immune system down-regulation or a systemic enhancer of immune system up-regulation in a combination therapeutic regimen.
Intralesional rose bengal chemoablative pharmaceutical composition
The intralesional chemoablative pharmaceutical composition comprises an intralesional chemoablative agent comprising rose bengal in an appropriate pharmaceutical composition, including an aqueous solution of rose bengal or a physiologically acceptable salt of rose bengal, administered intralesionally into the tumor.
Systemic inhibitor of immune system down-regulation
The systemic immunomodulatory anticancer agent is a systemic inhibitor of immune system down-regulation, including anti-CTLA-4 antibodies.
Overall claim coverage concentrates on combining intralesional chemoablation using a rose bengal-based intralesional chemoablative pharmaceutical composition with a systemic immunomodulatory anticancer agent that modulates immune system down-regulation or immune system up-regulation. The dependent coverage further narrows the systemic immune modulation direction and an anti-CTLA-4 antibody embodiment.
Stated Advantages
Local rapid tumor disruption exposing intact antigens to elicit a bystander antitumor immune response.
Reducing tumor-driven immune suppression.
Achieving synergy or additive effects in combination therapy.
Documented Applications
Treatment of a melanoma in a human.
Treatment of primary or metastatic liver cancer in a human.
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