Back to Sloan-Kettering Institute: Research Programs

Sloan-Kettering Institute // David Y. Gin

David Y. Gin: Synthesis of Complex Glycoconjugate Adjuvants for Anti-Cancer and Anti-Viral Vaccine Therapies

Synthesis of Complex Glycoconjugate Adjuvants for Anti-Cancer and Anti-Viral Vaccine Therapies

The development of therapeutic vaccines often includes the use of synthetic small molecule antigen constructs to elicit immune response. However, many subunit antigen vaccines are less immunogenic than those employing attenuated microorganisms. As a result, they often require co-administration with an adjuvant or immunostimulating complex, a substance that is itself not necessarily immunogenic but functions in concert with the antigen to enhance/prolong immune response. Purified extracts from the bark of the South American tree, Quillaja saponaria Molina, exhibit remarkable adjuvant activity. Among the more active components of these extracts are several complex triterpene saponins, including QS-21A_api, which has emerged as one of the most promising adjuvants for immune response potentiation and dose-sparing in vaccine therapy. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV, and malaria are among the numerous maladies targeted in several recent and ongoing vaccine clinical trials using QS-21A_api as a critical adjuvant component for immune response augmentation.

Whereas the design of subunit antigen constructs has played an influential role in the development of clinically viable vaccine therapies, efficacy modulation of vaccines through the design and chemical synthesis of distinct molecular adjuvants has been comparatively less common given the structural complexity of these substances. With the aid of several chemical glycosylation methodologies developed in our laboratories, we have achieved the first synthesis and structure verification of QS-21A_api. Additionally, the synthesis and structure verification of other potent immunostimulatory constituents of Quillaja saponaria, such as QS-7, are underway. Through collaborations with immunologists and clinicians, current efforts are also devoted to the generation of designed structural analogs for the development of more powerful and stable adjuvants for both anti-cancer and anti-viral therapeutic vaccines. As a consequence, we are in a unique position to conduct systematic structure-activity investigations on this class of natural product with the goal of unraveling its as yet unknown mechanism of immunostimulatory activity.

antigen (AN-tih-jen)

Any substance that causes the body to make a specific immune response.

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

attenuated (uh-TEN-yoo-way-ted)

Weakened or thinned. Attenuated strains of disease-causing bacteria and viruses are often used as vaccines. The weakened strains are used as vaccines because they stimulate a protective immune response while causing no disease or only mild disease in the person receiving the vaccine.

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

breast (brest)

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

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)

chemical (KEH-mih-kul)

A substance made up of elements, such as hydrogen or sodium.

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)

efficacy (EH-fih-kuh-see)

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

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

HIV

The cause of acquired immunodeficiency syndrome (AIDS). Also called human immunodeficiency virus.

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

immune response (ih-MYOON reh-SPONTS)

The activity of the immune system against foreign substances (antigens).

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

lung (lung)

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

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

melanoma (MEH-luh-NOH-muh)

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

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

molecule (MAH-leh-kyool)

The smallest particle of a substance that has all of the physical and chemical properties of that substance. Molecules are made up of one or more atoms. If they contain more than one atom, the atoms can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms.

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

potentiation (poh-TEN-shee-AY-shun)

In medicine, the effect of increasing the potency or effectiveness of a drug or other treatment.

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

prostate (PROS-tayt)

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

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)

synthetic (sin-THEH-tik)

Having to do with substances that are man-made instead of taken from nature.

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

therapeutic (THAYR-uh-PYOO-tik)

Having to do with treating disease and helping healing take place.

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)

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)