title: Generation of tumor-targeted antibody-CpG conjugates.
abstract: A number of monoclonal antibodies against tumor-associated antigens have been developed for the treatment of cancer. The anti-tumor effects of such antibodies can be enhanced by conjugation to immune stimulatory ligands, such as the toll-like receptor 9 agonist CpG oligodeoxynucleotides (CpG). The present study describes methods for the conjugation of CpG to two clinically approved monoclonal antibodies (rituximab and trastuzumab) via a Sulfo-EMCS maleimide linker. This conjugation method yielded stable joining of CpG and antibody (molar range 2.2-4.3:1). Immunofluorescence studies showed intact antigen-specific antibody binding of the immunoconjugates, that were comparable to unmodified antibody. Furthermore, antibody-CpG conjugates demonstrated improved (rituximab) or equivalent (trastuzumab) immune stimulatory activity compared to free CpG in vitro. These studies demonstrate the feasibility of antibody-CpG immunoconjugates and provide the foundation for future in vivo immunotherapy evaluation.
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Li
authors.forename: Julie K
authors.initials: JK
authors.lastname: Jang
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Lechner
authors.forename: Peisheng
authors.initials: P
authors.lastname: Hu
authors.forename: Leslie
authors.initials: L
authors.lastname: Khawli
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Scannell
authors.forename: Alan L
authors.initials: AL
authors.lastname: Epstein
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000737:chemistry; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000737:chemistry*; D019169:Jurkat Cells; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000737:chemistry; D000069283:Rituximab; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; C408982:CPG-oligonucleotide; D018796:Immunoconjugates; D009838:Oligodeoxyribonucleotides; D000069283:Rituximab; D000068878:Trastuzumab