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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.

Importance of Avidity for an Endogenous Drug Carrier: An Antibody Carrier for CpG Oligonucleotides