Office of Technology Development

Novel Method to Promote Thymic Rejuvenation Following Thymic Insult

SK2011-015

Summary of Invention

Dr. van den Brink and his colleagues have demonstrated that IL-22 promotes thymic rejuvenation following thymic insult. The thymus is the organ that produces and 'educates' T-cells, the major cell type of the adaptive immune system. Thymopoiesis is a highly complex process involving interactions between developing thymocytes and their supporting stromal microenvironment, namely thymic epithelial cells. Thymic epithelial cells are susceptible to damage from a variety of insults, including organ and bone marrow transplantation, chemotherapy and radiotherapy, complications related to HIV/AIDS, the natural aging process, malnutrition, and radiation poisoning due to nuclear disaster. Damage to thymic epithelial cells increases the rate of thymic atrophy, reducing the capacity of the thymus to educate maturing T- cells, and ultimately compromises immune function.

Currently, there are no effective clinical interventions to promote in vivo restoration and rejuvenation of thymic function following insult. The inventors have addressed this unmet need by demonstrating that systemic administration of recombinant IL-22 following thymic insult promotes the growth of the thymic epithelial cells critical to thymic rejuvenation and, thereby overcomes thymic atrophy and restores proper immune function.

Advantages

Mitigates iatrogenic immune effects associated with organ or bone marrow transplantation and with Enlarge Image chemotherapy or radiotherapy for cancer, thereby allowing more patients to benefit from such therapies.

Areas of Application

Therapy in the setting of:
- organ or bone marrow transplantation,
- chemotherapy or radiotherapy for cancer,
- complications related to HIV/AIDS,
- the natural aging process,
- malnutrition,
- radiation poisoning due to nuclear disaster;
Restoration of bone marrow function;
Vaccine adjuvant to boost T-cell production in response to vaccination in immunocompromised patients.

Stage of Development

In vivo proof-of-concept established in two mouse models of thymic injury: total body irradiation and syngeneic bone marrow transplantation;
Work in progress supports the use of IL-22 to restore bone marrow function;
Initial proof-of-concept work underway for use of IL-22 as a vaccine adjuvant.

Lead Inventor

Marcel van den Brink, MD, PhD

Intellectual Property Status

U.S. provisional patent application pending

Contact Information

Lisa Placanica, PhD
Tel: 212-639-6181; Fax: 212-717-3439
placanil@mskcc.org

Categories

Therapeutics

administration (ad-MIH-nih-STRAY-shun)

In medicine, the act of giving a treatment, such as a drug, to a patient. It can also refer to the way it is given, the dose, or how often it is given.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

bone marrow (bone MAYR-oh)

The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

bone marrow transplantation (bone MAYR-oh tranz-plan-TAY-shun)

A procedure to replace bone marrow that has been destroyed by treatment with high doses of anticancer drugs or radiation. Transplantation may be autologous (an individual's own marrow saved before treatment), allogeneic (marrow donated by someone else), or syngeneic (marrow donated by an identical twin).

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

cell (sel)

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

chemotherapy (KEE-moh-THAYR-uh-pee)

Treatment with drugs that kill cancer cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

clinical (KLIH-nih-kul)

Having to do with the examination and treatment of patients.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

epithelial (eh-pih-THEE-lee-ul)

Refers to the cells that line the internal and external surfaces of the body.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

immune function (ih-MYOON FUNK-shun)

Production and action of cells that fight disease or infection.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

immune system (ih-MYOON SIS-tem)

The complex group of organs and cells that defends the body against infections and other diseases.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

immunocompromised (IH-myoo-noh-KOM-proh-mized)

Having a weakened immune system caused by certain diseases or treatments.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

irradiation (ih-RAY-dee-AY-shun)

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic irradiation uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called radiation therapy and radiotherapy.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

malnutrition (mal-noo-TRIH-shun)

A condition caused by not getting enough calories or the right amount of key nutrients, such as vitamins and minerals, that are needed for health. Malnutrition may occur when there is a lack of nutrients in the diet or when the body cannot absorb nutrients from food. Cancer and cancer treatment may cause malnutrition.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

organ (OR-gun)

A part of the body that performs a specific function. For example, the heart is an organ.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

radiation (RAY-dee-AY-shun)

Energy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

radiation poisoning (RAY-dee-AY-shun POY-zuh-ning)

Serious illness caused by being exposed to high doses of certain types of radiation, usually over a short period of time. Symptoms of radiation poisoning usually occur right after exposure but they may happen over time, and they may come and go. Symptoms include nausea and vomiting, diarrhea, headache, dizziness, weakness, fatigue, bleeding, hair loss, swelling, itching, and redness of the skin, and other skin problems. Very large doses of radiation may cause death. Also called acute radiation sickness, acute radiation syndrome, radiation sickness, and radiation sickness syndrome.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

radiotherapy (RAY-dee-oh-THAYR-uh-pee)

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiotherapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiation therapy.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

recombinant (ree-KOM-bih-nunt)

In genetics, describes DNA, proteins, cells, or organisms that are made by combining genetic material from two different sources. Recombinant substances are made in the laboratory and are being studied in the treatment of cancer and for many other uses.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

response (reh-SPONTS)

In medicine, an improvement related to treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

syngeneic (SIN-jeh-NAY-ik)

Having to do with individuals or tissues that have identical genes. For example, identical twins and cells and tissues from them are syngeneic.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

systemic (sis-TEH-mik)

Affecting the entire body.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

therapy (THAYR-uh-pee)

Treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

thymus (THY-mus)

An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

transplantation (tranz-plan-TAY-shun)

A surgical procedure in which tissue or an organ is transferred from one area of a person’s body to another area, or from one person (the donor) to another person (the recipient).

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

vaccination (VAK-sih-NAY-shun)

Treatment with a vaccine.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

vaccine (vak-SEEN)

A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)

vaccine adjuvant (vak-SEEN A-juh-vunt)

A substance added to a vaccine to improve the immune response so that less vaccine is needed.

Source: The National Cancer Institute's Dictionary of Cancer Terms
(http://www.cancer.gov/dictionary)