Research: Laboratory Program
David V. Gold, Ph.D.

Dr. Gold is the Director of Laboratory Administration and is a Full Member at GSCC. He received his Ph.D. from SUNY at Stony Brook in 1977, working with Dr. Frederick Miller on one of the first reported biochemical and immunochemical studies of colonic mucins. He has been with GSCC from the start having brought numerous NCI funded projects to the Center in the fields of mucin biochemistry and immunology.

The long-range objective of Dr. Gold's research efforts is the development of monoclonal antibodies having clinical utility for the detection, diagnosis, and therapy of gastrointestinal cancers. Prior laboratory studies have shown that mucins, at least within the gastrointestinal system, have carbohydrate and peptide structures that are recognized as tissue-specific. Dr. Gold's group has generated and characterized several monoclonal antibodies that demonstrate relatively specific organ reactivity. Current work emphasizes the development of organ/tumor specific antibodies to be used for pancreatic cancer. The PAM4 antibody was generated against a pancreatic tumor-derived mucin (1). Except for a weak, yet positive reaction with normal gut epithelium, this antibody proved to be non-reactive with normal adult tissues, including normal adult pancreas. Greater than 85% of pancreatic cancer specimens are reactive with this antibody. As one of several projects, Dr. Gold's group is currently investigating the application of PAM4 in a new diagnostic test for the early detection of pancreatic cancer.

¹³¹Iodine-radiolabeled PAM4 was shown to target human pancreatic tumors grown as xenografts in mice (2) and importantly in initial groups of patients (3,4). Of 10 patients administered radiolabeled PAM4 antibody, specific tumor targeting was observed in 8. One of the non-targeted patients was later confirmed to have had pancreatitis and not pancreatic cancer, thus supporting the specificity of the PAM4 antibody. The other negative patient had a poorly differentiated cancer that did not express the target antigen.

Studies on the use of ¹³¹Iodine- and ⁹⁰Yttrium-radiolabeled PAM4 antibody for therapy [radioimmunotherapy, (RAIT)] of pancreatic cancer have shown that when used alone, a single administration of the maximum tolerated dose can provide significant extended survival of mice bearing large pancreatic tumors (5). Studies in progress are designed to examine the combined modality approach of employing gemcitabine and PAM4-radioimmunotherapy for synergistic anti-tumor effect (6).

1. Gold DV, Modrak DE, Ying Z, Cardillo, T.M, Sharkey RM and Goldenberg DM. A new MUC1 serum immunoassay differentiates pancreatic cancer from pancreatitis. J. Clin. Oncol. 2: 252-8 (2006).
2. Modrak DE, Cardillo, T.M, Newsome G, Goldenberg DM and Gold DV. Synergistic interaction between sphingomyelin and gemcitabine potentiates ceramide-mediated apoptosis in pancreatic cancer. Cancer Research 64: 8405-10 (2004).
3. Cardillo TM, Karacay H, Goldenberg DM, Yeldell D, Chang C-H, Modrak DE, Sharkey RM and Gold DV. Improved targeting of pancreatic cancer: experimental studies of a new bispecific antibody, pretargeting enhancement system for immunoscintigraphy. Clin.. Cancer Research, 10: 3552-61 (2004).
4. Gold DV, Schutsky K, Modrak DE and Cardillo TM. Low-dose radioimmunotherapy (90Y-PAM4) combined with gemcitabine for the treatment of experimental pancreatic cancer. Clinical Cancer Research 9: 3929s-37s (2003).
5. Gold DV, Juweid M, Cardillo T, Goldenberg DM, and Sharkey RM. Localization of pancreatic cancer with monoclonal antibody PAM4. Crit Rev Oncol Hematol 39: 147-154 (2001).
6. Mariani G, Molea N, Bacciardi D, Boggi U, Fornaciari G, Campani D, Salvadori PA, Giulianotti PC, Mosca F, Gold DV, Sharkey RM, and Goldenberg DM. Initial tumor targeting, biodistribution, and pharmacokinetic evaluation of the monoclonal antibody PAM4 in patients with pancreatic cancer. Cancer Res 55: 5911s-5915s (1995).