Methods of permeabilizing the blood brain barrier
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12208066-B2
Publication Date
2025-01-28
Expiration Date
Abstract
The present invention relates to using monoterpene or sesquiterpene to permeabilize the blood brain barrier.
Core Innovation
The invention relates to permeabilizing the blood-brain barrier (BBB) using monoterpenes and sesquiterpenes, including perillyl alcohol (POH) and NEO100, to enable delivery of therapeutic agents across the BBB for treatment of central nervous system (CNS) cancer. The approach is described as disrupting tight junctions to allow penetration of therapeutic agents into the CNS.
The document describes a method of treating CNS cancer by administering POH in relation to therapeutic agents, including chimeric antigen receptor T-cell (CAR-T) cells. The therapeutic agent delivery is enabled by co-administering POH and CAR-T, with the administration timing described as POH administered before or concurrently with the therapeutic agent.
The examples described include administration of NEO100/POH with intracardiac delivery to open the BBB and increase CNS delivery of therapeutic agents. Reported outcomes include enhanced antibody penetration and improved delivery of CAR-T cells and other therapeutics into CNS tumor models, including malignant glioma and intracranial lymphoma xenografts.
Claims Coverage
The provided claims content includes one independent claim directed to a CNS cancer treatment method that administers perillyl alcohol (POH) and CAR-T cells by intracardiac injection. The claim set is further narrowed by dependent features including POH dosing, POH-to-CAR-T timing, specific CAR-T targets, concurrent pharmaceutical composition, and addition of radiation.
Intracardiac POH with CAR-T for CNS cancer treatment
A method of treating a central nervous system (CNS) cancer in a mammal by administering perillyl alcohol (POH) before or concurrently with a therapeutic chimeric antigen receptor T-cell (CAR-T cell), wherein the POH and CAR-T cells are administered by intracardiac injection.
CNS cancer types matched to the intracardiac POH–CAR-T method
The method of intracardiac POH and CAR-T cell administration is limited to CNS cancer comprising malignant glioma, pilocytic astrocytomas (grade I), meningiomas, metastatic brain tumors, or pituitary adenomas.
POH dose range for intracardiac POH–CAR-T treatment
POH is administered at a dose from about 0.050 mg/kg to about 500 mg/kg body weight.
POH-to-CAR-T administration interval
POH is administered from about 0.2 minutes to about 60 minutes before administering the CAR-T cell.
Specific CAR-T targeting entities
The CAR-T cell is a CD19 CAR-T cell or a Lym-1 CAR-T cell.
Concurrent co-formulation in a pharmaceutical composition
POH and CAR-T cells are administered together in a pharmaceutical composition.
Combination with radiation
The method further includes treating the mammal with radiation.
Coverage centers on administering POH with therapeutic CAR-T cells via intracardiac injection to treat specified CNS cancers. Dependent features further specify POH dosing, a POH-to-CAR-T timing window, CAR-T targeting entities, concurrent administration as a pharmaceutical composition, and the option to add radiation.
Stated Advantages
Enables delivery of therapeutic agents across the BBB by disrupting tight junctions and increasing penetration into the CNS.
Enhances CNS delivery of antibodies and improves penetration of CAR-T cells into CNS tumor models.
Improves survival in glioma models when CAR-T delivery is facilitated by NEO100.
Supports delivery of CAR-T cells to intracranial tumor xenografts.
Documented Applications
Treatment of CNS cancers including malignant glioma and other brain tumor types using POH/NEO100 to permeabilize the BBB and facilitate delivery of CAR-T cells and antibodies across the BBB.
Facilitating delivery of therapeutic antibodies into the CNS via BBB opening after intracardiac administration of NEO100/POH.
CAR-T delivery to intracranial lymphoma xenografts using BBB opening facilitated by NEO100.
Delivery of dopamine to the CNS described in the document as enhanced by BBB opening facilitated by NEO100/POH.
Use of prior clinical observations of intranasal POH in recurrent malignant gliomas and related imaging context described in the document.
Interested in licensing this patent?