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Miami Transplant Institute

Miami Transplant Institute

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Liver and Gastrointestinal Transplantation Projects

Project 1: Immunotherapy with Natural Killer Cells for Patients that Receive a Liver Transplant Due to Liver Cancer

PROJECT SUMMARY:

Liver transplantation has emerged as one of the few curative treatment modalities for patients’ medications that decrease the immune defenses so that the body can accept the new liver. If patients do not receive these medications, their body will reject the new liver. Due to the fact that the body’s immune defenses are suppressed by the anti-rejection medications after the transplant, there is a risk that some cancer cells that still exist in the body may multiply and then liver cancer may recur.

During the transplant procedure the old liver that has cancer, is removed and is sent to pathology. According to the extent of the disease in the removed liver, an oncologist may prescribe prophylactic chemotherapy after the transplant to decrease the chances of disease recurrence.

GOAL:
The aim of this study is to try an additional form of treatment that might decrease the chances of disease recurrence. This form of treatment is the infusion of a particular type of cells, called Natural Killer (NK) cells extracted from the donor liver. Natural killer cells are a type of lymphocytes (white blood cells) that are present in the blood and play a role in the defense of the organism. In laboratory experiments it has been shown that when we place these cells together with cancer cells, the natural killer cells can attach to the cancer cells and kill them. Experimental evidence shows that Natural Killer cells can kill liver cancer cells they come in contact with.

Where to find Natural Killer Cells:
At the time that the transplant team is harvesting the new liver from the donor, they will also collect the donor’s Natural Killer cells. During the procurement of the liver from the donor, the organ is flushed with a sterile solution to flush away all the blood cells and prepare the organ for the transplant. This solution will be collected at the time of organ recovery. The cells that are in this solution will be purified, and Natural Killer cells will be extracted from the solution, cultured and activated.

Soon after the transplant, (3 days after the transplant), the Natural Killer cells will be collected from the culture and will be infused in the patient through a peripheral vein.

We will study liver cancer patients that have received a liver transplant. They will be also be followed by an oncologist and will receive the standard prophylactic treatment (chemotherapy) for cancer, as indicated by their oncologist. Half of them, the study group, will also receive this Natural Killer cell infusion. After the transplant, all patients will undergo frequent monitoring to detect the recurrence of liver cancer. We will compare the outcome of the patients in the study group versus the patients that received only the standard of care treatment.

This form of therapy is called immunotherapy. It is different from chemotherapy which is usually a synthetic compound toxic for all our organs. In this treatment we use natural cells of the body that can increase the defenses of our immune system and attack only the cancer cells like a smart bomb, sparing the rest of the organism.

Significance:

This immunotherapy will improve the outcome of patients that receive a liver transplant as a treatment for liver cancer.

Project 2: A New Family of Drugs to Prevent and Treat Rejection

PROJECT SUMMARY:

What is an aptamer?

Aptamers are very small molecules that we can synthesize in the lab. We use aptamers, as carriers to transport a specific medication or agent to specific cells. When we create an aptamer, we can design it in a way that it can bind to a specific cell with great specificity. The aptamer will bind to only the cells we want and not to anything else. At the same time we can create the aptamer to bind also to a specific medication or substance. Using this method we can transport the medication to specific cells. This method is currently used extensively in cancer patients, where with the use of aptamers we can direct chemotherapy agents directly to the cancer cells and spare the rest of the organs from the toxicity of the treatment (smart bomb concept).

What is rejection?

During a rejection episode in transplant patients, blood cells of the patient (lymhocytes B and T) attack the transplanted organ (liver or kidney) and destroy it. This process is called a rejection. This is a normal defense of our body. It happens because the lymphocytes perceive the transplanted organ as foreign and want to destroy it. Once the lymphocytes recognize the organ as foreign, they go through a process of activation and destroy it.

GOAL:

The goal of this project is to develop a clinically feasible strategy to eliminate activated B and T lymphocytes during episodes of rejection.

The approach is to use a carrier that can transport cytotoxic agents directly to the activated lymphocytes and destroy them. This carrier is created in the lab and is called an aptamer. We create a specific aptamer that can attach only to activated lymphocytes.

Then we attach to this aptamer a substance than can destroy these lymphocytes. By injecting the aptamer carrying the killer substance in the patient it binds to the lymphocytes, destroys them and stops the process of rejection.

We plan to test this experimental approach to an animal model: Heart transplant and skin grafts in mice. We prefer to use mice as they are the standard model to study immunology processes. Additionally our lab has extensive experience in microsurgery procedures in this model.

Clinical Research

Clinical Research in the Miami Transplant Institute includes basic laboratory and clinical research within our three main divisions: Kidney and Pancreas, Liver and Gastrointestinal and Heart and Lungs transplant.

The overall mission of our research is to study novel immunosuppressive treatments in order for our transplanted patients to attain a better quality of live after transplantation: reducing the side effects of medications, as well as reducing the incidence of transplant rejection after cadaveric or living-related donor transplants.

Clinical trials are organized within the other two groups under the direction of Dr. George Burke for the Kidney and Pancreas Program and Dr. Andreas Tzakis for the Liver and GI program.

Our research is funded under different sources; institutional, government/agency and industry

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