Differing sensitivity of non-hematopoietic human tumors to synergistic anti-transferrin receptor monoclonal antibodies and deferoxamine in vitro. 1995

J Kovar, and P W Naumann, and B C Stewart, and J D Kemp
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.

We tested non-hematopoietic human tumors for in vitro sensitivity to either a pair of synergistic IgG antitransferrin (Tf) receptor monoclonal antibodies (MAbs), deferoxamine (DFO) or the combination thereof. With an equimolar mixture of the two MAbs (A27.15, E2.3), two prostate tumors showed similar degrees of maximal growth inhibition (PC-3: 35%, DU 145: 38%), two breast tumors showed more variability (MDA-MB-231: 26%, SK-BR-3: 52%) and two neuroblastomas showed the most variability (SK-N-SH: 4%, SK-N-MC: 76%). When the MAbs were applied together with DFO, the D50 for DFO was reduced for all tumors (PC-3: 2.5x, DU 145: 3.7x; MDA-MB-231: 2.9x, SK-BR-3: 1.9x, and SK-N-SH: 2.6x, SK-N-MC: 7.0x). Sensitivity to MAbs was more closely correlated with the relative decrease in Tf receptor density resulting from antibody exposure than with initial receptor density. The degree of reduction of D50 for DFO resulting from the joint application with the MAbs was, however, most closely related to the growth rate of the tumors. Since some non-hematopoietic tumors exhibit sensitivity to the effects of a synergistic pair of IgG anti-Tf receptor MAbs and DFO, it appears that further preclinical studies with such tumors, especially those with higher Tf densities, would be of interest.

UI MeSH Term Description Entries
D008297 Male Males
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D009447 Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51) Neuroblastomas
D011471 Prostatic Neoplasms Tumors or cancer of the PROSTATE. Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D011990 Receptors, Transferrin Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released. Transferrin Receptors,Transferrin Receptor,Receptor, Transferrin
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D003676 Deferoxamine Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form. Desferrioxamine,Deferoxamine B,Deferoxamine Mesilate,Deferoxamine Mesylate,Deferoxamine Methanesulfonate,Deferoximine,Deferrioxamine B,Desferal,Desferioximine,Desferrioxamine B,Desferrioxamine B Mesylate,Desferroxamine,Mesilate, Deferoxamine,Mesylate, Deferoxamine,Mesylate, Desferrioxamine B,Methanesulfonate, Deferoxamine
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal

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