• Introduced
Bacille Calmette-Guérin (BCG), the
tuberculosis vaccine, into experimental cancer research as a way to stimulate non-specific resistance to tumor growth. BCG was FDA-approved in 1991 and is now widely used as a first line treatment for superficial
bladder cancer (1959). • Discovered the first linkage between the major histocompatibility complex (MHC) and disease—mouse leukemia—opening the way for the recognition of the importance of the MHC in the
immune response (1964). • Identified the first cell surface antigens distinguishing cells of different lineages, introducing the concept of cell surface antigens that could differentiate different
cell types. First coined TL (for “
thymus-
leukemia” antigen in mice) then later as the Ly series (originally named Ly-A and Ly-B and later called Ly-1, Ly-2, and Ly-3), this discovery led directly to the wide use of cell surface markers to distinguish and classify normal and
malignant cells and the development of CD classification (for “clusters of differentiation”). Most notably, Dr. Old discovered the LY-B antigen, later renamed CD8 in humans. CD8 cells, often referred to as “killer”
T cells, are one of the major cells of the adaptive immune response, and are capable of directly killing dangerous or foreign cells (1964–1968). • Discovery of the association between Epstein-Barr Virus (EBV) and nasopharyngeal cancer (1966). • Discovery of
tumor necrosis factor (TNF), a key immune signaling molecule (
cytokine) that, in addition to its promise for the treatment of cancer and other diseases, has provided a powerful research tool in
biomedicine (nearly 88,000 articles in
PubMed as of May 25, 2011) (1975). • Identification (independently, along with two other groups) of the
p53 protein, the
gene for which is mutated in approximately 50 percent of cancers (1979). • Conducting of the most comprehensive
dissection of the cell surface of human cancers using
monoclonal antibodies, with the identification of an array of cell surface antigens as targets for antibody-based therapies of human cancer. Of the monoclonal antibodies developed in Dr. Old's laboratory, thirteen have been licensed and seven are in clinical trials. These include: • MORAb-003 (
farletuzumab), currently in a phase III trial for ovarian cancer sponsored by Morphotek, which licensed the antibody from LICR. MORAb-003 targets the
folate receptor alpha, which is overexpressed on a number of
epithelial cancers, including
ovarian, breast,
renal, lung,
colorectal and brain cancers. • the anti-EGFr antibody Hu806, which
Abbott Laboratories acquired exclusive world-wide rights to develop in a major licensing deal in 2008. Hu806 targets the overexpressed form of the
epidermal growth factor receptor (EGFr) present in 50 percent of all cancers of epithelial origin. • cG250 (
girentuximab, Rencarex®/Redectane®), which targets the CA-IX molecule/G250 antigen, expressed on over 90 percent of clear cells renal cell carcinomas (RCC,
kidney cancer), and is in phase III clinical trials as a diagnostic tool and as a therapeutic modality (also iodine-131-G250). • hu3S193, which targets the LeY antigen, an
oligosaccharide epitope expressed on
glycolipids and
glycoproteins by a wide range of epithelial cancers, is in phase II clinical trials being conducted by LICR spin-off company Recepta Biopharma. • huA33, which targets the
A33 antigen present on colorectal cancer cells. The antibody has been licensed to LICR spin-off company Life Sciences Pharmaceuticals, and the mAb's therapeutic potential is being tested as a stand-alone antibody, as a radioimmunotherapy agent, and in combination with
chemotherapy. • Establishment of the
autologous typing system as the methodology leading to the identification of the first specific human tumor antigens recognized by
antibodies and T cells, created 150 separate
cancer cell lines, and laid the groundwork for the development of SEREX by Pfreundschuh in 1995. • Discovery and naming of several members of the
CT (cancer/testis) family of human tumor antigens, including New York-ESO-1 (NY-ESO-1).
NY-ESO-1 is one of the most immunogenic human tumor antigens discovered to date and is expressed in approximately 35 percent of
melanomas, 30 percent of
breast cancers, 30 percent of
liver cancers, 25 percent of
lung cancers, less than five percent of
colon cancers. • Contribution to the resurrection of the cancer
immunosurveillance hypothesis and to the development of the expanded model of
cancer immunoediting. • Establishment in 2001 of the
Cancer Vaccine Collaborative (CVC), the world's first network of
clinical trial sites closely linked with immunological monitoring laboratories with the goal to develop effective therapeutic cancer vaccines by first understanding the fundamental immunological implications of
vaccination and applying that knowledge toward the rational design of optimal vaccine formulations. A joint program of the Cancer Research Institute and Ludwig Cancer Research, the CVC conducts parallel, early phase, single variable clinical trials of various
cancer vaccine formulations and combinations composed of cancer-specific antigen, immunological adjuvant, vaccine delivery platforms, and modulators of
immune suppression. • Founder of "The Academy of Cancer Immunology [which] was established in 1998 to advance understanding of the role of immunity in cancer and to recognize outstanding achievements in the field of cancer immunology. The Academy currently has 53 members from 11 countries and holds annual elections for Academy membership." ==Leadership==