Nanotargeted Curcumin to Suppress Cancer Cell Growth

We are studying the effect of targeted delivery of Curcumin to antigen presenting cells in the immune system. Our study seeks to determine if delivery of Curcumin can suppress tumor growth for human colon cancer as well as other cancers. This study is examining tumor responses to Curcumin when given alone or in combination with an immune Checkpoint Inhibitor. Positive results will lead to our applications for Fast-Track FDA human and companion pet animal cancer trials.

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 being developed by Rodos Biotarget GmbH, the CLR-TargoSphere®, that delivers encapsulated drugs exclusively to antigen presenting cells of the immune system. We have reformulated Curcumin into our nanocarrier, enabling us to bypass oral and systemic distribution and deliver contents directly to myeloid Dendritic Cells (mDCs) to promote induction of Programmed Death (PD-1 positive) anti-tumor Cytotoxic T-Lymphocytes and enable restoration of immunity.

The significance of this study:

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. Nanocarrier-targeted delivery of Curcumin to the mDCs circumvents these problems and delivers concentrated drug directly to immune cells associated with restoration of tumor dysregulation, as well as directly to the tumor.

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

We are conducting a preclinical study in a colon cancer model at the Charles River Labs in North Carolina and examining the response to treatment in 9 groups of 10 animals treated with combinations of a range of three dosages of curcumin, with and without a standard dose of an approved Immune Checkpoint Inhibitor. Subsequently, an additional group will be studied for PK/PD analyses and distribution to systemic organs to be submitted to the FDA for approval for clinical trials.

All preclinical treatments and analyses are being conducted at the Charles River Preclinical Research Organization in North Carolina, USA.