Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas

Blood
Hans-Peter GerberIqbal S Grewal

Abstract

Despite major advances in the treatment of non-Hodgkin lymphoma (NHL), including the use of chemotherapeutic agents and the anti-CD20 antibody rituximab, the majority of patients eventually relapse, and salvage treatments with non-cross-resistant compounds are needed to further improve patient survival. Here, we evaluated the antitumor effects of the microtubule destabilizing agent monomethyl auristatin E (MMAE) conjugated to the humanized anti-CD19 antibody hBU12 via a protease-sensitive valine-citrulline (vc) dipeptide linker. hBU12-vcMMAE induced potent tumor cell killing against rituximab-sensitive and -resistant NHL cell lines. CD19 can form heterodimers with CD21, and high levels of CD21 were reported to interfere negatively with the activity of CD19-targeted therapeutics. However, we observed comparable internalization, intracellular trafficking, and drug release in CD21(low) and CD21(high), rituximab-sensitive and -refractory lymphomas treated with hBU12-vcMMAE. Furthermore, high rates of durable regressions in mice implanted with these tumors were observed, suggesting that both rituximab resistance and CD21 expression levels do not impact on the activity of hBU12-vcMMAE. Combined, our data suggest that hBU12-vcMMAE may...Continue Reading

References

Sep 1, 1994·Immunology Today·T F TedderP Engel
Oct 1, 1993·The Journal of Experimental Medicine·A K MatsumotoD T Fearon
Apr 21, 1997·The Journal of Experimental Medicine·H T Maecker, S Levy
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·M A GhetieE S Vitetta
Aug 15, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·P McLaughlinB K Dallaire
Jun 3, 2000·Annual Review of Immunology·D T Fearon, M C Carroll
Aug 30, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·T A DavisR Levy
Mar 5, 2003·Leukemia & Lymphoma·Peiguo G ChuLawrence M Weiss
Apr 30, 2003·Seminars in Oncology·J F San MiguelA Orfao
Jun 5, 2003·Nature Biotechnology·Svetlana O DoroninaPeter D Senter
Oct 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kevin J HamblettJoseph A Francisco
Dec 9, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Che-Leung LawAlan F Wahl
Dec 23, 2004·Endocrine-related Cancer·Paul CarterMaureen Ryan
Sep 13, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David G Maloney
Sep 22, 2005·Bioconjugate Chemistry·Michael M C SunStephen C Alley
Oct 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Norihito YazawaThomas F Tedder
Mar 17, 2006·Applied Immunohistochemistry & Molecular Morphology : AIMM·Rania M SeliemRobert P Hasserjian
Apr 20, 2006·Nature Reviews. Immunology·Paul J Carter
Jul 13, 2006·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Risto S Cvetković, Caroline M Perry
May 11, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M Fey, M Fey
Sep 27, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·V AgneseA Russo
Mar 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Scott H OlejniczakMyron S Czuczman
Mar 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Myron S CzuczmanFrancisco J Hernandez-Ilizaliturri

❮ Previous
Next ❯

Citations

Sep 4, 2012·Cancer Immunology, Immunotherapy : CII·Ahmad TradJoachim Grötzinger
Jul 11, 2012·Pharmaceutical Research·Gary D Stack, John J Walsh
Apr 29, 2010·Current Hematologic Malignancy Reports·Malcolm A Smith
Nov 13, 2012·Journal of Hematology & Oncology·Michael A Firer, Gary Gellerman
Jan 11, 2013·Arthritis Research & Therapy·Henrik E MeiThomas Dörner
Nov 2, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Suzanne L TopalianDrew M Pardoll
Mar 1, 2011·Therapeutic Delivery·Victor S Goldmacher, Yelena V Kovtun
Mar 1, 2012·Pharmaceutical Patent Analyst·Benedikt SammetNorbert Sewald
Feb 6, 2014·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Christos Vaklavas, Andres Forero
Feb 22, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hernan CarolRichard B Lock
Jan 8, 2016·British Journal of Cancer·Nikolaos Diamantis, Udai Banerji
Dec 15, 2010·Expert Opinion on Investigational Drugs·Andrew G PolsonVanitha Ramakrishnan
Mar 13, 2010·Cancer Treatment Reviews·Jean Pierre Bourquin, Shai Izraeli
Oct 15, 2009·Hematology/oncology Clinics of North America·Syed A AbutalibWendy Stock
Apr 23, 2013·Therapeutic Advances in Hematology·Christos Vaklavas, Andres Forero-Torres
Mar 11, 2018·Artificial Cells, Nanomedicine, and Biotechnology·Meghdad Abdollahpour-AlitappehMahdi Habibi-Anbouhi
Sep 25, 2018·Journal of Cellular Physiology·Meghdad Abdollahpour-AlitappehMohsen Abolhassani
Feb 8, 2018·Journal of Experimental & Clinical Cancer Research : CR·Cécile Chalouni, Sophia Doll
May 28, 2019·Nature Biotechnology·Vivian H TrangMatthew R Levengood
Jul 17, 2015·Bioscience Reports·Christina Peters, Stuart Brown
Jun 27, 2020·Journal of Biomedical Science·Wen-Wei LinTian-Lu Cheng
Jul 26, 2018·Scientific Reports·M CascalhoJ L Platt
Oct 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Veronique BlancJohn M Lambert
Sep 19, 2012·Cancer Research·Joseph M TuscanoRobert T O'Donnell
Oct 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Vincent RibragBertrand Coiffier
Sep 23, 2018·Molecular Cancer Therapeutics·Christopher S NeumannPeter D Senter
Apr 1, 2021·Bioconjugate Chemistry·Jared T MillerL Nathan Tumey
Jul 27, 2021·Clinics in Laboratory Medicine·Ting Zhou, Hao-Wei Wang
May 16, 2017·Journal of Medicinal Chemistry·Zakey Yusuf BuuhRongsheng E Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.