Combination therapy for adult T-cell leukemia-xenografted mice: flavopiridol and anti-CD25 monoclonal antibody.

Blood
Meili ZhangThomas A Waldmann

Abstract

Adult T-cell leukemia (ATL) develops in a small proportion of individuals infected with human T-cell lymphotrophic virus-1. The leukemia consists of an overabundance of activated T cells, which express CD25 on their cell surfaces. Presently, there is no accepted curative therapy for ATL. Flavopiridol, an inhibitor of cyclin-dependent kinases, has potent antiproliferative effects and antitumor activity. We investigated the therapeutic efficacy of flavopiridol alone and in combination with humanized anti-Tac antibody (HAT), which recognizes CD25, in a murine model of human ATL. The ATL model was established by intraperitoneal injection of MET-1 leukemic cells into nonobese diabetic/severe combined immunodeficient mice. Either flavopiridol, given 2.5 mg/kg body weight daily for 5 days, or HAT, given 100 microg weekly for 4 weeks, inhibited tumor growth as monitored by serum levels of human beta-2-microglobulin (beta2mu; P < .01), and prolonged survival of the leukemia-bearing mice (P < .05) as compared with the control group. Combination of the 2 agents dramatically enhanced the antitumor effect, as shown by both beta2mu levels and survival of the mice, when compared with those in the flavopiridol or HAT alone group (P < .01). The...Continue Reading

References

Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C QueenT A Waldmann
Aug 1, 1985·The Journal of Clinical Investigation·T UchiyamaH Uchino
Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·R ClynesJ V Ravetch
Aug 15, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·P McLaughlinB K Dallaire
Mar 4, 2000·Journal of the National Cancer Institute·A M Senderowicz, E A Sausville
Mar 31, 2000·Nature Medicine·R A ClynesJ V Ravetch
Oct 29, 2000·Annals of the Rheumatic Diseases·J C Morris, T A Waldmann
Apr 20, 2001·Critical Reviews in Oncology/hematology·H H Sedlacek
Mar 22, 2002·Nature Reviews. Cancer·P Carter
Apr 17, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gary K SchwartzDavid Kelsen
Feb 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Meili ZhangThomas A Waldmann

❮ Previous
Next ❯

Citations

May 28, 2010·Journal of Clinical and Experimental Hematopathology : JCEH·Kimiru Uozumi
May 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Meili ZhangThomas A Waldmann
Jun 30, 2006·Expert Opinion on Biological Therapy·Eric Jacobsen, Ann LaCasce
Feb 18, 2011·The Journal of General Virology·Cecilia ParrulaStefan Niewiesk
Jun 10, 2014·Virus Research·M Cecilia M ParrulaStefan Niewiesk
Aug 30, 2008·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Anette WeyergangKristian Berg
Oct 5, 2010·Asia-Pacific Journal of Clinical Oncology·Chun-Wei LeeKung-Shen Chen
Nov 8, 2011·Lasers in Surgery and Medicine·Anette WeyergangKristian Berg
Apr 13, 2018·Frontiers in Microbiology·Sara MoodadHiba El Hajj
Aug 4, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kamal SharmaJohn C Morris
Sep 26, 2006·Best Practice & Research. Clinical Haematology·Nicola Gökbuget, Dieter Hoelzer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.