Abstract
A native form of mouse monoclonal IgG1 antibody called MAG-1, which recognizes an epitope on provasopressin, has been found to shrink and produce extensive necrosis of human breast tumor xenografts in nu/nu mice. We examined the ability of 90Yttrium-labeled and native MAG-1 to affect the growth in nu/nu mice of cancer xenografts that were estrogen-responsive (from MCF-7 cells) and triple-negative (from MDA-MB231 cells). The growth rates of treated cells were compared to those receiving saline vehicle and those receiving 90Yttrium-labeled and native forms of the ubiquitous antibody, MOPC21. Short-term treatments (4 doses over 6 days) not only with 90Yttrium-MAG-1 but also native MAG-1 produced large reductions in size of rapidly growing tumors of both types, while both 90Yttrium- MOPC21 and native MOPC21 had no effect. Native and 90Yttrium-MAG-1 effects were similar, and arrested tumors recommenced growing soon after treatments stopped. Increasing native MAG-1 treatment to single dosing for 16 consecutive days shrank tumors of both types with no regrowth apparent over a 20-day post-treatment period of observation. Pathological examination of such tumors revealed they had undergone very extensive (>66%) necrosis.
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Acknowledgment
This study was supported in part by USPHS SBIR Phase I Grant: 1R43CA119483-01 to Woomera Therapeutic Inc.
Conflict of interest statement
Concerning the signed COI, all authors with the exception of William G. North and Roy H.L. Pang have no commercial interest relating to the material in the manuscript. However, as explained in the referenced patent applicant and by institute designation, Drs. North and Pang do have a commercial interest in Woomera Therapeutics Inc., the patent applicant. Dr. North is a full-time faculty member of Dartmouth Medical School, but is also the President of Woomera Therapeutics Inc. and holds >40% interest in that company. Dr. Pang is the CEO and CSO of the company.
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North, W.G., Pang, R.H.L., Gao, G. et al. Native MAG-1 antibody almost destroys human breast cancer xenografts. Breast Cancer Res Treat 127, 631–637 (2011). https://doi.org/10.1007/s10549-010-1009-6
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DOI: https://doi.org/10.1007/s10549-010-1009-6