title: Importance of avidity for an endogenous drug carrier: an antibody carrier for CpG oligonucleotides.
abstract: In animal models, successful anticancer monotherapy with CpG oligodeoxynucleotide (ODN) has been limited to the intratumoral and peritumoral routes of administration. To overcome this limitation, we developed a delivery system utilizing an endogenous antibody as a carrier for CpG ODNs. When a 1:1 conjugate of 2,4-dinitrophenyl (DNP) to a CpG ODN was administered to tumor-bearing mice that were preimmunized against DNP, intravenous (iv) administration successfully inhibited tumor growth (Palma, E.; Cho, M. J. J. Controlled Release 2007, 120, 95-103). In the present studies, we reproduced the iv results and showed that a DNP derivative of a controlled ODN with scrambled nucleotide sequence failed in the same model. Perhaps more significantly, contralateral subcutaneous (sc) routes of administration also suppressed tumor growth. However, in a separate experiment, when the anti-DNP titer level was low, the antitumor effect was abolished, supporting the importance of the avidity involved in the complexation. With the low titer, a significant fraction of injected dose must have existed as unbound that is subject to rapid clearance. The present study justifies chemically cross-linked immune complexes such that the CpG ODN cannot dissociate in the body after administration.
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Cheung
authors.forename: Moo
authors.initials: M
authors.lastname: Cho
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy; D009578:Nitrobenzenes / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology
chemical_list: D000906:Antibodies; C408982:CPG-oligonucleotide; D004337:Drug Carriers; D009578:Nitrobenzenes; D009838:Oligodeoxyribonucleotides