Research: Laboratory Program –
Rhona Stein, Ph.D.

Dr. Stein is currently an Associate Member at GSCC. She received her Ph.D. from the University of Pittsburgh in 1977. She has been with GSCC since 1986 having several NCI and New Jersey Cancer commission funded projects.

Dr. Stein's group has generated and characterized several monoclonal antibodies that demonstrate relative specificity for a variety of tumor types with no or only limited reactivity with normal tissues (1). Extensive preclinical studies have been performed using monoclonal antibody RS7, which reacts with cancers of the lung, breast, ovaries, and prostate. Studies on the use of ¹³¹Iodine- and ⁹⁰Yttrium-radiolabeled RS7 antibody for therapy [radioimmunotherapy, (RAIT)] of lung and breast cancers have shown that when used alone, a single administration of the maximum tolerated dose can provide significant extended survival of mice bearing large tumors (2,3).

Studies in progress are focusing on means to improve the anti-tumor efficacy of radiolabeled monoclonal antibodies. The problem of increasing the radiation dose delivered by monoclonal antibodies to tumor cells is being tackled by developing a novel chemistry for the attachment of radioactive iodine to antibodies. Use of a new chemical linker causes the radioactive iodine to become trapped inside the tumor cells which in turn yields a markedly increased radiation dose to the tumor cells, and importantly without increasing radiation exposure of normal body tissues. Pre-clinical studies in an animal model of lung cancer have shown a significant increase in survival using this approach (4,5). Current work is directed at developing these agents for use in breast cancer and non-Hodgkin's lymphoma.

A second strategy for improving the anti-tumor efficacy of radiolabeled monoclonal antibodies involves combining chemotherapy with radioimmunotherapy. Dr. Stein's group has shown that combined modality therapy using a radioactively labeled monoclonal antibody against the tumor marker carcinoembryonic antigen in combination with chemotherapy augments the anti-tumor efficacy of either modality alone for medullary thyroid cancer, without a significant increase in toxicity (6).

1. Stein R, Chen S, Sharkey RM, and Goldenberg DM. Murine monoclonal antibodies raised against human non-small cell carcinoma of the lung: specificity and tumor targeting. Cancer Res 50: 1330-1336 (1990).
2. Stein R, Blumenthal RD, Sharkey RM, and Goldenberg DM. Comparative biodistribution and radioimmunotherapy of MAb RS7-3G11 and its F(ab')2 fragment in nude mice bearing human tumor xenografts. Cancer (Suppl.) 73: 816-823 (1994).
3. Shih L, Xuan H, Aninipot R, Stein R, and Goldenberg DM. In vitro and in vivo reactivity of an internalizing antibody, RS7, with human breast cancer. Cancer Res (Suppl.) 55:5857-5863 (1995).
4. Stein R, Goldenberg DM, Thorpe SR, Basu A, and Mattes MJ. Effects of radiolabeling monoclonal antibodies with a residualizing form of iodine on the accretion of radioisotope in tumors. Cancer Res 55: 3132-3139 (1995).
5. Stein R, Govindan SV, Chen S, Reed L, Spiegelman H, Griffiths GL, Hansen HJ, and Goldenberg DM. Successful therapy of a human lung cancer xenograft using MAb RS7 labeled with residualizing radioiodine. Crit Rev Oncol Hematol 39: 173-180 (2001).
6. Stein R, Chen S, Reed L, Richel H, and Goldenberg DM. Combining radioimmunotherapy and chemotherapy for treatment of medullary thyroid carcinoma: Effectiveness of dacarbazine. Cancer 94: 51-61 (2002).