Method and kit for treating a solid tumor and associated desmoplasia
Inventors
Assignees
Rosalind Franklin University of Medicine and Science
Publication Number
US-10028906-B2
Publication Date
2018-07-24
Expiration Date
2037-03-22
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Abstract
A kit for treating a human patient with a solid tumor with a desmoplasia associated therewith having: (1) a container of and effective amount of a CCNp37 (SEQ ID No. 37), CCNp38 (SEQ ID No. 38) or a combination of CCNp37 and CCNp38 (SEQ ID Nos. 37 and 38); (2) a container of an effective amount of a chemotherapeutic agent or an immunotherapeutic agent; and (3) instructions for administering these components which can involve a pretreatment with the CCNp37 (SEQ ID No. 37), CCNp38 (SEQ ID No. 38) or a combination of CCNp37 and CCNp38 (SEQ ID Nos. 37 and 38) to a patient in need thereof.
Core Innovation
The present invention provides a method and a kit for treating a human patient with a solid tumor associated with desmoplasia by combining an effective amount of CCNp37 (SEQ ID No. 37), CCNp38 (SEQ ID No. 38), or a combination of the two peptides, with a chemotherapeutic or immunotherapeutic agent. The kit includes containers for each component and instructions for administering them, which can involve pre-treatment with the peptides prior to administration of the chemotherapeutic or immunotherapeutic agent.
The problem addressed by this invention is the challenge of treating solid tumors with associated desmoplasia that limits the effectiveness of standard chemotherapeutic or immunotherapeutic agents. Prior art disclosed use of full-length CCN3 molecules or larger protein fragments for treatment of fibrosis or angiogenesis, but did not show that small CCN3-derived peptides, specifically CCNp37 and CCNp38, in combination with cancer therapies, could be used to treat tumors and their dense stromal reactions more effectively.
This approach encompasses administering the peptides either alone, in combination, or sequentially with standard cancer drugs such as gemcitabine or other listed agents, to reduce desmoplasia, improve drug penetration and effectiveness, and target tumor stroma. Both in vitro and in vivo results demonstrated that while the peptides themselves may not directly reduce cancer cell proliferation in vitro, they significantly impact tumor burden, desmoplasia, angiogenesis, and ascites formation in animal models when administered as part of the invention.
Claims Coverage
The patent includes three independent claims representing three primary inventive features.
Kit for treating a human with a solid tumor with desmoplasia
The kit comprises: - A container of an effective amount of CCNp37 (SEQ ID No. 37), CCNp38 (SEQ ID No. 38), or a combination of CCNp37 and CCNp38 (SEQ ID Nos. 37 and 38). - A container of an effective amount of a chemotherapeutic or immunotherapeutic agent. - Instructions for administering these components to a patient in need thereof.
Method of treating a human patient with a solid tumor with a desmoplasia associated therewith
The method includes: - Administering to the human patient one or both of the peptides of SEQ ID NO. 37 and/or 38. - Administering a chemotherapeutic agent or an immunotherapeutic agent to the patient.
Method for treating a desmoplasia associated with a solid tumor in a human patient
The method includes: - Administering to the patient an effective amount of CCNp37 (SEQ ID No. 37), CCNp38 (SEQ ID No. 38), or a combination of CCNp37 and CCNp38 (SEQ ID Nos. 37 and 38).
The inventive features focus on kits and methods combining CCNp37 and/or CCNp38 peptides with cancer drug therapies, either for treating solid tumors with desmoplasia or specifically targeting the reduction of desmoplasia associated with such tumors.
Stated Advantages
Peptides CCNp37 and CCNp38 in combination with chemotherapeutic or immunotherapeutic agents reduce tumor stroma/desmoplasia, thereby potentially allowing for lower dosing of conventional drugs and reducing their adverse side effects.
The peptides are much smaller than full-length proteins or larger fragments, likely making them easier to synthesize and formulate for delivery.
Reduction of desmoplasia and improved delivery of chemotherapeutic or immunotherapeutic agents can result in greater treatment effectiveness than with cancer drugs alone.
Combination therapy with peptides allows for reducing angiogenesis, ascites formation, and blocking metastasis of the solid tumor.
Kit and methods using these peptides were shown to be non-toxic in animal studies.
Documented Applications
Treatment of a solid tumor with associated desmoplasia in a human patient using a combination of CCNp37 and/or CCNp38 and a chemotherapeutic or immunotherapeutic agent.
Treatment of pancreatic cancer and other solid tumors, both benign and cancerous, more preferably those with associated desmoplasia.
Reduction of desmoplasia, angiogenesis, and ascites in solid tumors in vivo using CCNp37 and/or CCNp38.
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