title: Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20+B-cell lymphoma.
abstract: We developed a nano-antibody targeted chemotherapy (nATC) delivery strategy in which tumor specific and clinically relevant antibodies (rituximab, anti-CD20) are non-covalently bound to the albumin scaffold of nab-paclitaxel (ABX). We define the nanoparticle formed when the 2 drugs are bound (AR160). The newly created nATC retains the cytotoxicity of ABX and CD20 affinity of rituximab in vitro. We describe the binding characteristics of the ABX and rituximab in AR160 using peptide mapping/Biacore approach. Flow-based methods, including ImageStream and nanoparticle tracking, were used to characterize the AR160 particles in vitro. A mouse model of human B-cell lymphoma was utilized to test in vivo efficacy of AR160 therapy, which suggested improved tumor targeting (biodistribution) as the most likely mechanism of AR160 therapeutic superiority over ABX or rituximab alone. These data suggest a novel platform for nATC delivery using a slight modification of existing cancer drugs with significantly improved treatment efficacy.
authors.affiliation: Department of Oncology Research, Mayo Clinic, 200 1st St SW Rochester, MN 55905, USA.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Nevala
authors.affiliation: Department of Oncology Research, Mayo Clinic, 200 1st St SW Rochester, MN 55905, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Butterfield
authors.affiliation: Department of Oncology Research, Mayo Clinic, 200 1st St SW Rochester, MN 55905, USA.
authors.forename: Shari L
authors.initials: SL
authors.lastname: Sutor
authors.affiliation: Department of Oncology Research, Mayo Clinic, 200 1st St SW Rochester, MN 55905, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Knauer
authors.affiliation: Department of Oncology Research, Mayo Clinic, 200 1st St SW Rochester, MN 55905, USA.
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage*; D000069283:Rituximab / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018951:Antigens, CD20; D000972:Antineoplastic Agents, Phytogenic; D000069283:Rituximab; D017239:Paclitaxel