Multivalent rituximab lipid nanoparticles as improved lymphoma therapies: indirect mechanisms of action and in vivo activity

Author:

Popov Jesse12,Kapanen Anita I1,Turner Christopher1,Ng Rebecca1,Tucker Catherine1,Chiu Gigi1,Klasa Richard1,Bally Marcel B34,Chikh Ghania1

Affiliation:

1. Department of Experimental Therapeutics, British Columbia Cancer Agency, 675 West 10th Ave., Vancouver BC, V5Z 1L3, Canada

2. College for Interdisciplinary Studies, The University of British Columbia, 1855 West Mall, Vancouver BC, V6T 1Z2, Canada

3. Department of Pathology & Laboratory Medicine, Faculty of Medicine, The University of British Columbia, 2211 Wesbrook Mall, Vancouver BC, V6T 2B5, Canada.

4. Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver BC, V6T 1Z3, Canada

Abstract

Aims: The activity of therapeutic antibodies can be enhanced by creating multivalent constructs, such as antibody lipid nanoparticles (LNPs). Here, we examine differences between rituximab (Ritux) and Ritux-LNPs in terms of their indirect mechanisms of action: complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Materials & Methods: We employed two mantle-cell lymphoma cell lines, Z138 and JVM2, which exhibit different in vivo sensitivities to Ritux along with variable expression levels of cell-surface proteins that regulate ADCC and CDC. Results: In both cell lines, CDC and ADCC were found to be significantly enhanced after treatment with Ritux-LNPs compared with Ritux. In vivo efficacy studies, however, suggested that the therapeutic activities of Ritux and Ritux-LNPs were equivalent, which was subsequently explained in part by pharmacokinetic studies indicating rapid elimination of Ritux-LNP. Conclusion: Although indirect and direct mechanisms of multivalent Ritux are enhanced, its further development requires methods to improve its circulation lifetime.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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