title: Targeted drug delivery and cross-linking induced apoptosis with anti-CD37 based dual-ligand immunoliposomes in B chronic lymphocytic leukemia cells.
abstract: Despite advances in chemo and immunotherapeutic agents for B chronic lymphocytic leukemia (B-CLL), the undesirable adverse side effects due to non-specific cellular uptake remain to be addressed. We identified anti-CD37 monoclonal antibody immunoliposomes (ILs) as vehicles for targeted delivery to B chronic lymphocytic leukemia cells. To achieve maximal benefits for all patients, a new strategy of dual-ligand immunoliposomes (dILs) was developed. A combinatorial antibody microarray technology was adapted to quickly identify optimal antibody combinations for individual patient cells. For proof-of-concept, a B-cell specific antibody, either anti-CD19 or anti-CD20, was combined with anti-CD37 to construct dILs with enhanced selectivity and efficacy. Consistent with data from the antibody microarray, these dILs provided highly specific targeting to both leukemia cell lines and B-CLL patient cells. Compared with the single antibody ILs, the anti-CD19/CD37 dILs clearly demonstrated superior delivery efficiency and apoptosis induction to B-CLL patient cells, whereas the anti-CD20/anti-CD37 dILs were found to be the most efficient for delivery to leukemia cell lines. In addition, it was observed that anti-CD37 ILs without payload drug mediated effective CD37 cross-linking and induced potent apoptosis induction. The anti-CD19/CD20 dILs showed the improved cell apoptosis induction compared to either anti-CD19 ILs or anti-CD20 ILs. Our findings suggest that the dual-ligand ILs may provide a preferred strategy of personalized nanomedicine for the treatment of B-cell malignancies.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Mao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Chaofang
authors.initials: C
authors.lastname: Yue
authors.forename: Xinmei
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.forename: David
authors.initials: D
authors.lastname: Jarjoura
authors.forename: Michael E
authors.initials: ME
authors.lastname: Paulaitis
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
authors.forename: Natarajan
authors.initials: N
authors.lastname: Muthusamy
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D018941:Antigens, CD19 / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008081:Liposomes / Q000276:immunology*; D011409:Propylene Glycols / Q000008:administration & dosage* / Q000494:pharmacology; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D059470:Tetraspanins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; C059071:CD37 protein, human; D007166:Immunosuppressive Agents; D008081:Liposomes; D011409:Propylene Glycols; D059470:Tetraspanins; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine