Effects of neocarzinostatin-chimeric Fab conjugates on the growth of human pancreatic carcinoma xenografts

Abstract

Summary Neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of MAb A7 (chA7Fab) directed against human pancreatic carcinoma. The anti-tumour effect of chA7Fab-NCS was tested in a nude mouse model on pancreatic carcinoma and compared with A7-NCS or NCS alone. The antitumour effect of chA7Fab-NCS increased in a dose-dependent manner and was significantly greater than either A7-NCS or NCS. Tumour growth was completely suppressed after the administration of chA7Fab-NCS. An enzyme-linked immunosorbent assay with rabbit anti-mouse immunoglobulin was performed to examine the antigenicity of chA7Fab. ChA7Fab had less reactivity with rabbit anti-mouse immunoglobulin than either whole antibody A7 or murine Fab fragments of A7. Thus, chA7Fab-NCS can inhibit human pancreatic cancer growth in an animal and may be useful for targeting chemotherapy to pancreatic cancer in humans.

Application of 99mTc labeled chimeric Fab fragments of monoclonal antibody A7 for immunoscintigraphy of pancreatic carcinoma

“…The accuracy of diagnosis of digestive carcinoma has been remarkably improved by imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI). However, the prognosis of pancreatic carcinoma, one of the most lethal diseases, remains very poor [1]. One of the reasons for its poor prognosis is the difficulty of obtaining an early diagnosis of the pancreatic carcinoma.…”

DNA Cleavage/Repair and Signal Transduction Pathways in Irradiated Breast Tumor Cells

“…In addition, the chimeric Fab fragment was at least 600 times less antigenic than the original A7 antibody, as assessed by its reactivity with rabbit anti-mouse IgG serum. Subsequent studies with a chimeric Fab fragment conjugated to zinostatin showed that it was more effective than the original zinostatin-A7 conjugate (and much more effective than native zinostatin) in suppressing growth of HPC-YS xenografts [100].…”

Neocarzinostatin, Aptamer Conjugates for Targeting EpCAM-positive Tumor Cells

“…NCS antibody conjugates have been used for targeting pancreatic cancer (23) and melanoma (24) however due to the adverse reactions elicited in patients, stage II clinical trials were not continued (25). In order to overcome the immune responses elicited by earlier study, an aptamer was synthesized against EpCAM.…”