title: Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice.
abstract: Antibodies are considered as 'magic bullets' because of their high specificity. It is believed that antibodies are too large to routinely enter the cytosol, thus antibody therapeutic approach has been limited to extracellular or secreted proteins expressed by cancer cells. However, many oncogenic proteins are localized within the cell. To explore the possibility of antibody therapies against intracellular targets, we generated a chimeric antibody targeting the intracellular PRL-3 oncoprotein to assess its antitumor activities in mice. Remarkably, we observed that the PRL-3 chimeric antibody could efficiently and specifically reduce the formation of PRL-3 expressing metastatic tumors. We further found that natural killer (NK) cells were important in mediating the therapeutic effect, which was only observed in a nude mouse model (T-cell deficient), but not in a Severe Combined Immunodeficiency' (scid ) mouse model (B- and T-cell deficient), indicating the anticancer effect also depends on host B-cell activity. Our study involving 377 nude and scid mice suggest that antibodies targeting intracellular proteins can be developed to treat cancer.
authors.affiliation: Institute of Molecular and Cell Biology, A*STAR, 61 Biopolis Drive, Proteos, Singapore 138648, Republic of Singapore.
authors.forename: Ke
authors.initials: K
authors.lastname: Guo
authors.forename: Jing Ping
authors.initials: JP
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Jie
authors.forename: Abdul Qader O
authors.initials: AQ
authors.lastname: Al-Aidaroos
authors.forename: Cheng William
authors.initials: CW
authors.lastname: Hong
authors.forename: Cheng Peow Bobby
authors.initials: CP
authors.lastname: Tan
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Leyon
authors.initials: L
authors.lastname: Varghese
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Feng
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Zhou
authors.forename: Wee Joo
authors.initials: WJ
authors.lastname: Chng
authors.forename: Qi
authors.initials: Q
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D058990:Molecular Targeted Therapy / Q000379:methods*; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D017874:Immediate-Early Proteins; C111534:Ptp4a3 protein, mouse; D011993:Recombinant Fusion Proteins; D017027:Protein Tyrosine Phosphatases