A comparison of targetting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients

Abstract

Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in neuroblastoma patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG uptake and provide a relatively low number of 6,300 binding sites/cell for mAb chCE7. Tumours were treated with single injections of 131I-MIBG (110 MBq) and with 131I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with 131I-chCE7, the subcutaneous tumours nearly disappeared; treatment with 131I-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumour regrowth delay of 9 days occurred with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35, which does not bind to SK-N-SH cells, compared with a regrowth delay of 34 days with 131I-mAb chCE7 and of 24 days with 131I-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the treatments. The superior growth inhibition achieved by 131I-chCE7 compared with 131I-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chCE7 with L1-CAM present in normal human tissues was investigated by direct binding of radioiodinated mAb to frozen tissue sections. Results showed a strong reaction with normal human brain tissue and weak but detectable binding to normal adult kidney sections. Seven patients with recurrent neuroblastoma were sequentially imaged with 131I-MIBG and 131I-chCE7. The results underlined the heterogeneity of neuroblastoma and showed the two imaging modalities to be complementary. 131I-chCE7 scintigraphy may have clinical utility in detecting metastases which do not accumulate 131I-MIBG, and the antibody may hold potential for radioimmunotherapy, either by itself or in combination with 131I-MIBG.

L1 Cell Adhesion Molecule Is a Novel Therapeutic Target in Intrahepatic Cholangiocarcinoma

“…the cancer. Recent reports have shown that L1 expression correlates with tumor progression and metastasis of several other carcinomas (18)(19)(20)(21)(22). However, L1 expression in ICC has not been previously reported.…”

“…L1 expression is found in other cell types such as lymphoid and myelomonocytic cells, kidney tubule epithelial cells, and intestinal crypt cells (13)(14)(15)(16)(17). Recent reports have shown that L1 is also expressed in several types of cancers, including colon carcinoma, ovarian and uterine carcinomas, malignant gliomas, recurrent neuroblastoma, cutaneous malignant melanoma, and renal cell carcinoma, and that its expression correlates with tumor progression and metastasis (18)(19)(20)(21)(22). However, L1 expression in ICC has not been reported.…”

Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma

“…Recently, L1CAM was investigated as target antigen for radioimmunotherapy in a mouse xenograft model of human neuroblastoma by use of a radio-labeled specific anti-L1CAM antibody (33). MENX-affected rats, because of the overexpression of L1CAM in their adrenal tumors, represent a good experimental model to evaluate the efficacy of radio-labeled anti-L1CAM antibodies for functional imaging and therapy of pheochromocytoma.…”

Hepatocyte Growth Factor-induced Ectodomain Shedding of Cell Adhesion Molecule L1

“…In contrast, high expression of L1 was found in 8 of 12 renal tumor cell lines and in some renal tumors (2). 2 It was shown that the cell-bound form of L1 can serve as a target for radioimmunodiagnosis of metastatic neuroblastoma (4), and L1 may also be a marker and therapeutic target for certain renal cancers.…”