Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model

Abstract

BackgroundDespite the numerous applications of monoclonal antibodies (mAbs) in cancer therapeutics, animal models available to test the therapeutic efficacy of new mAbs are limited. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice are one of the most highly immunodeficient strains and are universally used as a model for testing cancer-targeting mAbs. However, this strain lacks several factors necessary to fully support antibody-mediated effector functions—including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity (CDC)—due to the absence of immune cells as well as a mutation in the Hc gene, which is needed for a functional complement system.MethodsWe have developed a humanized mouse model using a novel NSG strain, NOD.Cg−Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG−Hc1), which contains the corrected mutation in the Hc gene to support CDC in addition to other mechanisms endowed by humanization. With this model, we reevaluated the anticancer efficacies of nanoencapsulated rituximab after xenograft of the human Burkitt lymphoma cell line 2F7-BR44.ResultsAs expected, xenografted humanized NSG−Hc1 mice supported superior lymphoma clearance of native rituximab compared with the parental NSG strain. Nanoencapsulated rituximab with CXCL13 conjugation as a targeting ligand for lymphomas further enhanced antilymphoma activity in NSG−Hc1 mice and, more importantly, mediated antilymphoma cellular responses.ConclusionsThese results indicate that NSG−Hc1 mice can serve as a feasible model for both studying antitumor treatment using cancer targeting as well as understanding induction mechanisms of antitumor cellular immune response.

Chemokine-targeted nanoparticles: stimulation of the immune system in cancer immunotherapy

“…Conjugation of CK CXCL13 to nanoencapsulated rituximab as a targeting ligand in lymphomas further enhanced the tumoricidal potential in xenografted humanized non-obese diabetic (NOD)-SCID-gamma-hemolytic complement (NSG-Hc 1 ) mice by augmenting anti-lymphoma cellular responses. Conjugation of CXCL13 over the surface of nanoencapsulated rituximab results in efficient targeting of lymphoma in the brain [118]. Zhao et al [119] devised a new method delivering an immune active NP called erythrocyte-anchored systemic immunotherapy (EASI), capable to colocalize with the metastatic lung cancer cells following dislodging from the erythrocyte surface.…”

Rapid prototyping of functional acoustic devices using laser manufacturing

“…This cell line was subcloned from the human 2F7 Burkitt NHL cell line, which was retrieved from a patient with AIDS-lymphoma. 50 2F7 cells are cultured in Iscove's Modified Dulbecco's Medium (IMDM), a modification of Dulbecco's Modified Eagle Medium, supplemented with 10% (vol/vol) fetal bovine serum (FBS, ThermoFisher Scientific) and 1% penicillin/streptomycin (mediatech). 2F7 cells are seeded in T25 Nunclon Sphera Flasks (ThermoFisher Scientific) at a concentration of 5 × 10 5 cells per mL and are kept in T25 Nunclon Sphera Flasks (ThermoFisher Scientific) in an incubator at 37 °C and 5% CO 2 .…”