Back to Journals » International Journal of Nanomedicine » Volume 10 » Issue 1

Construction and characterization of an anti-CD20 mAb nanocomb with exceptionally excellent lymphoma-suppressing activity

Authors Li H, Wu C, Chen T, Zhang G, Zhao H, Ke C, Xu Z,

Received 31 December 2014

Accepted for publication 15 May 2015

Published 30 July 2015 Volume 2015:10(1) Pages 4783—4796

DOI https://doi.org/10.2147/IJN.S80129

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang

Hua-Fei Li,1–3,* Cong Wu,4,* Ting Chen,5,* Ge Zhang,1 He Zhao,1 Chang-Hong Ke,1 Zheng Xu2

1International Joint Cancer Institute, Translation Medicine Institute, 2Planning Division, Scientific Research Department, 3Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, 4Department of Laboratory Diagnosis, Changhai Hospital, 5Department of Cardiology, Changhai Hospital, the Second Military Medical University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Abstract: The CD20-directed monoclonal antibody rituximab (RTX) established a new era in the treatment of non-Hodgkin lymphoma (NHL); however, suboptimal response and/or resistance to RTX still limit its clinical merits. Although four effector mechanisms are validated to participate in CD20-based immunotherapy, including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, caspase-dependent apoptosis, and lysosome-mediated programmed cell death (PCD), they could hardly be synchronously activated by any anti-CD20 mAb or mAb derivative until now. Herein, a novel mAb nanocomb (polyethylenimine polymer–RTX–tositumomab [PPRT nanocomb]) was firstly constructed through mass arming two different anti-CD20 mAbs (RTX and tositumomab) to one polymer by nanotechnology. Comparing with free mAbs, PPRT nanocomb possesses a comparable binding ability and reduced “off-rate” to surface CD20 of NHL cells. When treated by PPRT nanocomb, the caspase-dependent apoptosis was remarkably enhanced except for concurrently eliciting complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and lysosome-mediated PCD. Besides, “cross-cell link”-assisted homotypic adhesion by PPRT nanocomb further enhanced the susceptibility to PCD of lymphoma cells. Pharmacokinetic assays revealed that PPRT nanocomb experienced a relatively reduced clearance from peripheral blood compared with free antibodies. With the cooperation of all the abovementioned superiorities, PPRT nanocomb exhibits exceptionally excellent in vivo antitumor activities in both disseminated and localized human NHL xenotransplant models.

Keywords: non-Hodgkin lymphoma, CD20, nanotechnology, rituximab, programmed cell death

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model

Boechat AL, Oliveira CP, Tarragô AM, Costa AG, Malheiro A, Guterres SS, Pohlmann AR

International Journal of Nanomedicine 2015, 10:6603-6614

Published Date: 22 October 2015

Imaging of Hsp70-positive tumors with cmHsp70.1 antibody-conjugated gold nanoparticles

Gehrmann MK, Kimm MA, Stangl S, Schmid TE, Noël PB, Rummeny EJ, Multhoff G

International Journal of Nanomedicine 2015, 10:5687-5700

Published Date: 8 September 2015

Emerging and future therapies for hemophilia

Carr ME, Tortella BJ

Journal of Blood Medicine 2015, 6:245-255

Published Date: 3 September 2015

Molecular targets in arthritis and recent trends in nanotherapy

Roy K, Kanwar RK, Kanwar JR

International Journal of Nanomedicine 2015, 10:5407-5420

Published Date: 26 August 2015

A new recombinant factor VIII: from genetics to clinical use

Santagostino E

Drug Design, Development and Therapy 2014, 8:2507-2515

Published Date: 12 December 2014

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010