Abstract
Antibody-based therapy revolutionized medicine with its inception some 40 years ago. There are now some 100 monoclonal antibody treatments approved by the Federal Drug Administration (FDA) for treating anything from cancer to infectious diseases (1). Because of their high degree of sensitivity to precise target antigens they are accomplished reagents for basic research, diagnostics and therapeutics, making up nearly 20% of the FDA's new drug approvals each year. Advances in antigen discovery, the different molecular origins (rodent, human, exotic), isolation (cell-based, phage-base) and manufacturing have all contributed to their forefront status. These various aspects are still being evaluated to better meet the demand of antibody-based therapeutics (2).
As we continue our 40th year celebration of the founding of our Journal and “Why Hybridomas” are important, Magdalena Blaszczyk-Thurin provides us with a perspective of the studies that began to emerge from the Biotech powerhouse of the Wistar Institute that focused on the exquisite beauty of monoclonal antibodies. Many of today's modern cancer immunotherapy approaches owe their conceptual basis to Hilary Koprowski's team's pioneering work conducted at the Wistar Institute of Anatomy and Biology in Philadelphia, Pennsylvania starting in the late 70s. At the Wistar, Dr. Thurin's research focused on the structural and functional characterization of carbohydrate antigens and application for diagnosis including Sialyl-Lewis A (SA-LeA) that became a diagnostic test for pancreatic and colon cancer (CA19-9).
Importantly, the studies at the Wistar provided the basis of many of the newest approaches to cancer therapy that target glycans such as the neolactoseries antigen Lewis Y, the gangliosides GD2/GD3 and Epidermal Growth Factor Receptor (3) and summarized in Dr. Thurin's Perspective. The worked provided linking antigen discovery with antibody functionality forming the basis for the identification of tumor associated glycans using monoclonal antibodies, the use of monoclonal antibodies in passive cancer therapy, the development and use of anti-idiotypic antibodies tested in clinical trials and the development of mimetics based upon antibody structure to elicit antigen targeting antibodies. The Wistar with its collaborators was among the first institutions to test antibodies in the clinic (4, 5). Not only did the Wistar contribute to the antibody discovery process but they had their own antibody manufacturing/purification facility to rapidly test new found antibodies in the Lab in the clinic.
The ensemble of the results and the achievements at the Wistar proved that the synergy between the generation of monoclonal antibodies (6) with various disciplines, such as immunology (7), structural biology (8-10), cancer biology (11), and oncology (12, 13), was a successful approach before the multidisciplinary team concept in science was developed and pursued. These achievements fueled a venue that became a center of gravity for outstanding cancer research investigators where discoveries were made that set the foundations for the new wave of clinically applicable agents and the long-lasting contribution to cancer research and patient care were made.