This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rittmann-Grauer, L. S. Articles by Mackensen, D. G. Search for Related Content PubMed PubMed Citation Articles by Rittmann-Grauer, L. S. Articles by Mackensen, D. G.

Reversal of Vinca Alkaloid Resistance by Anti-P-Glycoprotein Monoclonal Antibody HYB-241 in a Human Tumor Xenograft

Hybritech Incorporated, San Diego, California 92121

A panel of monoclonal antibodies (MAbs) to P-glycoprotein was developed by immunization of mice with multidrug-resistant human neuroepithelioma and neuroblastoma cells. All the anti-P-glycoprotein MAbs reacted with the extracellular portion of P-glycoprotein. The MAbs were examined for their ability to enhance accumulation of actinomycin D, vincristine, vinblastine, and doxorubicin in the human mdr1 transfectant cell line, BRO/pFRmdr1.6. HYB-241, an IgG₁ anti-P-glycoprotein MAb, was the most effective modulator, increasing actinomycin D levels in the transfectant line by 6-fold, vincristine by 2-fold, and vinblastine levels by 3-fold. None of the MAbs were capable of modifying the accumulation of doxorubicin. HYB-241 lowered the 50% inhibitory concentration values of actinomycin D by 11-fold, vincristine by 6-fold, and vinblastine by 2-fold. No effect on the 50% inhibitory concentration values of doxorubicin or gramicidin were seen. ¹¹¹In-labeled HYB-241 localized in human tumor xenografts of BRO/pFRmdr1.6 in nude mice (25% injected dose/g at 120 h). Mice with established drug-resistant xenografts were treated with antibody 24 h prior to the injection of Vinca alkaloid at concentrations known to be non-growth inhibitory. The addition of HYB-241 at 25 mg/kg per injection prior to drug resulted in a significant inhibition of growth of this drug-resistant tumor.

¹ To whom requests for reprints should be addressed, at Hybritech, Inc., P. O. Box 269006, San Diego, CA 92126.

Received 8/27/91. Accepted 1/24/92.

This article has been cited by other articles:

				K. Goda, F. Fenyvesi, Z. Bacso, H. Nagy, T. Marian, A. Megyeri, Z. Krasznai, I. Juhasz, M. Vecsernyes, and G. Szabo Jr. Complete Inhibition of P-glycoprotein by Simultaneous Treatment with a Distinct Class of Modulators and the UIC2 Monoclonal Antibody J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 81 - 88. [Abstract] [Full Text] [PDF]

				S.-J. Kim, H. Uehara, S. Yazici, J. E. Busby, T. Nakamura, J. He, M. Maya, C. Logothetis, P. Mathew, X. Wang, et al. Targeting platelet-derived growth factor receptor on endothelial cells of multidrug-resistant prostate cancer. J Natl Cancer Inst, June 7, 2006; 98(11): 783 - 793. [Abstract] [Full Text] [PDF]

				M. H. Frank, M. D. Denton, S. I. Alexander, S. J. Khoury, M. H. Sayegh, and D. M. Briscoe Specific MDR1 P-Glycoprotein Blockade Inhibits Human Alloimmune T Cell Activation In Vitro J. Immunol., February 15, 2001; 166(4): 2451 - 2459. [Abstract] [Full Text] [PDF]