Translational research: in vivo testing of cryoablation and non-toxic products as a therapeutic treatment for metastatic breast cancer

Info

Location: Albert Einstein College of medicine of Yeshiva University, New York, USA
Collaboration: Claudia Gravekamp, PhD

 
This project has been closed and the summary is currently being updated.

 

Cryoablation is a process that uses extreme cold to kill cancer cells by going with a needle into the tumor. It is a widely used treatment for specific localized cancer types and particularly used when surgery is not an option.

Tumor cell death by cryoablation is induced by the formation of intracellular crystals that cause tissue damage and the release of proteins called tumor-associated antigens (TAA). These antigens, in turn, may stimulate specific white blood cells of the immune system to kill tumor cells in metastases. However, the immune system in the tumor environment is always suppressed. Therefore, there is a need for agents that can reduce this immune suppression in the tumor environment in order for cryoablation to be able to induce an immune response and to have a better effect on the metastases.

In previous research studies we found that curcumin or cyclic di-guanylate (c-di-GMP) are both able to reduce immune suppression. We have tested combinations of cryoablation and curcumin, c-di-GMP or other non-toxic products in mice with metastatic breast cancer. The results of the combination with Meriva, a curcumin food supplement with enhanced bioavailability, have been published in May 2015 (abstract).

The final goal is to select the most promising combination of cryoablation and one or more non-toxic products, test this combination as soon as possible in clinical trials and make it available for patients.

This project is financed by Reliable Cancer Therapies.

Professional info

Location: Albert Einstein College of medicine of Yeshiva University, New York, USA
Collaboration: Claudia Gravekamp, PhD

 

This project has been closed and the summary is currently being updated.

 

Cryoablation is a process that uses extreme cold to kill cancer cells. It is a widely used treatment for specific localized cancer types and particularly for metastatic cancer. Tumor cell death by cryoablation is induced by the formation of intracellular crystals that causes tissue damage and the release of tumor-associated antigens (TAA). These antigens, in turn, may stimulate T cells to kill tumor cells in metastases that express the tumor-associated antigen. Since the immune system in the tumor microenvironment is always suppressed, the stimulation of T cells by cryoablation further impairs any helpful immune system productivity. Therefore, there is a need for agents that can reduce this immune suppression in the tumor environment in order for cryoablation to be able to induce the release of tumor-associated antigens. For instance, tumor cells and immune cells, such as myeloid-derived suppressor cells (MDSC) and macrophages, inhibit T cell responses in the tumor microenvironment by producing high levels of cytokines. Interleukin (IL)-6 is one of those cytokines and frequently produced in patients with breast cancer, ovarian cancer, lung cancer, and other types of cancers.

In previous research studies we found that reduction of IL-6 by anti-IL-6 antibodies or curcumin (Indian spice known for reducing the production of IL-6) restored T cell responses to tumor-associated antigen (TAA) Mage-b in vitro and in vivo.

The specific aims of this project are to test cryoablation in combination with several non-toxic products in a mouse model of metastatic breast cancer (4T1 model) and analyze T-cell responses after treatment. The results of the combination with Meriva, a curcumin food supplement with enhanced bioavailability, have been published in May 2015 (abstract).

The final goal is to select a promising combination of cryoablation and one or more non-toxic products and test this combination as soon as possible in clinical trials and make it available for patients.

This project is financed by Reliable Cancer Therapies.