Successful therapy of a human lung cancer xenograft using MAb RS7 labeled with residualizing radioiodine.
We have recently reported that a radioiodinated, DTPA-appended peptide, designated IMP-R1, is a residualizing iodine label that overcomes many of the limitations that have impeded the development of residualizing iodine for clinical use. In this study the potential of 131I-IMP-R1-RS7, an internalizing anti-EGP-1 monoclonal antibody, was evaluated by performing preclinical therapy studies in nude mice bearing Calu-3 human non-small cell carcinoma of the lung xenografis. Elimination of 6 of 9 established tumors (mean tumor volume=0.3 cm(3)) was observed using a single dose of 350 microCi/mouse of 131I-IMP-R1-RS7, with all animals tolerating the dose. At the same dose and specific activity of 131I-RS7, labeled using the conventional chloramine-T method, there were four deaths, and one complete remission in nine treated mice. At the maximum tolerated dose of conventionally 131I-labeled RS7, 275 microCi, mean stable disease for approximately 5 weeks was observed, with no complete responses. Specificity of the therapeutic effect was shown in an isotype-matched control experiment, where 131I-IMP-R1-RS7 was markedly more effective than the (131)I-IMP-R1-labeled control antibody. These studies demonstrate that (131)I-IMP-R1-RS7 provides a therapeutic advantage in comparison to conventional 131I-labeled RS7, as predicted by the increased tumor accretion observed previously in targeting studies. A direct comparison of the maximum tolerated doses of (131)I-IMP-R1-RS7 (350 microCi) and 90Y-DOTA-RS7 (105 microCi) was performed in this tumor model using large established tumors (mean tumor volume=0.85 cm(3)). Anti-tumor efficacy and toxicity of the two treatments were comparable.
Stein
R
R
Garden State Cancer Center, 520 Belleville Avenue, Belleville, NJ 07109, USA. rstein.gscancer@att.net
Govindan
S V
SV
Chen
S
S
Reed
L
L
Spiegelman
H
H
Griffiths
G L
GL
Hansen
H J
HJ
Goldenberg
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use; D008175:Lung Neoplasms; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000379:methods / Q000592:standards; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D008565:Membrane Proteins