With eight other NFCR research centers at universities and research hospitals worldwide, the NFCR Center at Dana-Farber will conduct therapeutic antibody research and provide high affinity human single-chain antibodies (sFv) to facilitate the ongoing cancer research of NFCR scientists. Many of the most promising anti-cancer drugs developed in recent years utilize humanized or human monoclonal antibodies – Rituximab (anti-CD20); Herceptin (anti-Her2); Campath-H (anti-CD52). Other NFCR Centers have been established at Oxford, Yale, Penn State, University of California-Berkeley, University of Arizona, Freie Universität Berlin, and the Institute of Medicinal Biotechnology in Beijing.
"This new initiative allows one of the world's strongest research programs at Dana-Farber to be networked into a collaborative partnership with NFCR scientists internationally. This collaborative effort adds a new dimension to NFCR's 'Laboratory Without Walls'," said Dr. Michael Wang, Director of Research at the National Foundation for Cancer Research in Bethesda, Maryland. "With this new NFCR Center for Therapeutic Antibody Engineering at Dana-Farber, we hope to create great synergies and multiple possibilities toward our goal of curing cancer."
How the Center Works
Traditionally, monoclonal antibodies have been derived from mouse models. However, this technique can produce Human Anti-mouse Antibody Responses (HAMA) when used clinically for human therapies. Recently, alternative methods, including Phage Display, have been developed to bypass those problems.
The Phage Display method uses genetically engineered phage, a kind of bacterial virus, to produce human antibody. Marasco's laboratory at Dana-Farber has constructed a non-immune human single-chain antibody phage display library, the "Mehta library." The quality of a phage library depends on its size. Marasco's library contains 15 billion antibody phages; each one phage has a different antibody gene incorporated into its DNA and displays the encoded antibody on its surface. The significant size of this library makes it possible to quickly isolate antibodies against virtually any cancer target, including the ones that are usually very hard to isolate (highly phylogentically conserved or poorly immunogenic). With this high quality phage display library, Marasco will be able to provide high affinity monoclonal antibodies to NFCR scientists around the world to support their basic cancer research and/or clinical studies for the treatment of certain cancers.
Wayne Marasco, MD, PhD
Wayne Marasco, MD, PhD, is a specialist in immunochemistry and infectious diseases at the Dana-Farber Cancer Institute and Harvard Medical School in Boston. As a member of the faculty in the Department of Cancer Immunology and AIDS, Marasco has dedicated many years of study to retroviruses such as HIV, which causes AIDS, and HTLV-1, which causes Adult T-cell Leukemia. Marasco was one of a small group of researchers who pioneered the idea that intracellular antibodies "intrabodies" could reach the inside of the cell to fight retroviruses. In 1993, Marasco was the first to demonstrate that an intrabody could block a virus protein inside a cell, and this approach is now being applied to halt the spread of HIV and to block the action of cancer causing oncoproteins. "We are pleased to be a critical and vital link among the worldwide network of NFCR sponsored scientists to find new monoclonal antibody drugs," said Marasco. "We believe in the value of exploring every avenue in our quest to cure cancer, and with this partnership between NFCR and the Dana-Farber, we are closer to that goal."
National Foundation for Cancer Research Since its founding in 1973, the National Foundation for Cancer Research has spent more than $180 million funding basic science cancer research to understand how and why cells become cancerous. This worldwide "laboratory without walls" assembles the intellectual power to achieve one of medicine's greatest goals: a cure for cancer--all types of cancer. Prevention, new treatments, and a cure depend on understanding cancer's genetic origins; NFCR is dedicated to funding scientists who are discovering cancer's molecular mysteries and translating these discoveries into therapies that hold the only real hope for curing cancer. NFCR is Research for a Cure. For more information, please visit NFCR's website at www.NFCR.org or call 800-321-CURE.
Dana-Farber Cancer Institute
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), a designated comprehensive cancer center by the National Cancer Institute.