About This Project

We hypothesize that targeted delivery of Curcumin to antigen presenting cells in the immune system can suppress tumor growth for a variety of cancers. This study will examine tumor responses to Curcumin in a colon cancer mouse model when given alone or in combination with an FDA-approved immune Checkpoint Inhibitor. Positive results will lead to Fast-Track FDA applications for human and companion pet animal cancer trials.

Ask the Scientists

What is the context of this research?

Curcumin has been shown in numerous studies to have a variety of antiproliferative activities, but is limited clinically because of poor oral absorption and bio-availability. Our team had previously invented a nanocarrier, the CLR-TargoSphere, that delivers encapsulated drugs exclusively to antigen presenting cells of the immune system. We reformulated Curcumin into our nanocarrier, enabling us to bypass oral and systemic distribution and deliver contents directly to myeloid Dendritic Cells to promote induction of Programmed Death (PD-1 positive) anti-tumor Cytotoxic T-Lymphocytes and enable restoration of immunity.

What is the significance of this project?

A hallmark of all cancers is an ability to adopt various strategies to escape immune surveillance. Curcumin enables tumor regression by a variety of mechanisms which include restoration of CD4+/CD8+ T cell populations, reversal of Type 2 cytokine bias, reduction of the Treg population, suppression of T cell apoptosis, and induction of PD-1 positive Cytotoxic T-Lymphocytes.

Major drawbacks to clinical use is its poor solubility, inability to be absorbed orally, rapid metabolism, and reduced systemic bioavailability.

Delivery of Curcumin directly to Antigen Presenting Cells in this study allows an objective evaluation of its efficacy in a tumor bearing animal.

What are the goals of the project?

We have designed a preclinical research study in a colon cancer mouse model to begin October 2017 at the Charles River Labs in North Carolina. We will examine the response to treatment in 5 groups of 6 animals treated with combinations of high dose curcumin, low dose curcumin, with and without a standard dose of an FDA-approved Checkpoint Inhibitor. An additional group will be studied for PK/PD analyses. and biodistribution to systemic organs and the brain and spinal cord. One last group will be untreated and act as controls.

All treatment and analyses will be conducted at the Charles River Preclinical Research Organization in North Carolina, USA.