Differing sensitivity of non-hematopoietic human tumors to synergistic anti-transferrin receptor monoclonal antibodies and deferoxamine in vitro.
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.
Kovar
J
J
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
Naumann
P W
PW
Stewart
B C
BC
Kemp
J D
JD
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy; D003676:Deferoxamine / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D009447:Neuroblastoma / Q000473:pathology / Q000628:therapy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy; D011990:Receptors, Transferrin / Q000276:immunology* / Q000378:metabolism; D017262:Siderophores / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D011990:Receptors, Transferrin; D017262:Siderophores; D003676:Deferoxamine