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Novel clinical approaches in monoclonal antibody-based management in colorectal cancer patients: Radioimmunoguided surgery and antigen augmentation

✍ Scribed by Mario Roselli; Oreste Buonomo; Antonina Piazza; Fiorella Guadagni; Aldo Vecchione; Ercole Brunetti; Cesidio Cipriani; Giuseppe Amadei; Carol Nieroda; John W. Greiner; Carlo U. Casciani


Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
60 KB
Volume
15
Category
Article
ISSN
8756-0437

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✦ Synopsis


Surgery, the most effective treatment for colon and rectal cancer, is based on empirical knowledge of the patterns of tumor spread, gross findings at laparotomy, and histologic confirmation of tumor-free margins. In spite of the many technical improvements in surgery, there has not been a significant change in cure rates for colon and rectal cancers. In fact, one-half of affected patients will not survive 5 years. It is in this arena of treatment for primary colon and rectal cancer patients that radioimmunoguided surgery (RIGS) technology may provide the most benefit. RIGS is an intraoperative procedure for detection of carcinoma lesions that are targeted with a radiolabeled monoclonal antibody (MAb) to provide the surgeon with immediate intraoperative definition of tumor margins and identification of occult disease. To optimize this technique, our studies were designed to increase tumor uptake by higher affinity CC-49 (a second-generation MAb) and to increase tumor antigen expression using biological response modifiers (BRMs). The ability of BRMs, such as interferons (IFNs), to enhance the expression of tumor-associated antigens, may play an important role in an adjuvant setting for MAb-based treatment. Preclinical and clinical data provided evidence for the use of IFN as an adjuvant to enhance MAb-targeting of human carcinoma lesions. A combination protocol with IFN and RIGS is ongoing at our institution.


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## Abstract Biparatopic CEA, carcinoembryonic antigen (MAb) was newly designed and tested as to whether it enhanced the accuracy of tumor detection by reducing non‐specific binding in experimental radioimmunoguided surgery. Biparatopic MAb was prepared by using cross‐linking of reduced Fab′ fragmen