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Title: Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice
Authors: Guo, K.
Tang, J.P.
Jie, L.
Al-Aidaroos, A.Q.O.
Hong, C.W.
Tan, C.P.B.
Park, J.E.
Varghese, L.
Feng, Z.
Zhou, J. 
Chng, W.J.
Zeng, Q. 
Keywords: Antibody therapy
Intracellular oncoprotein
PRL-3 monoclonal antibody
PRL-3 mouse/human chimeric antibody
Issue Date: Feb-2012
Source: Guo, K.,Tang, J.P.,Jie, L.,Al-Aidaroos, A.Q.O.,Hong, C.W.,Tan, C.P.B.,Park, J.E.,Varghese, L.,Feng, Z.,Zhou, J.,Chng, W.J.,Zeng, Q. (2012-02). Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice. Oncotarget 3 (2) : 158-171. ScholarBank@NUS Repository.
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 suggests that antibodies targeting intracellular proteins can be developed to treat cancer. © Zeng et al.
Source Title: Oncotarget
ISSN: 19492553
Appears in Collections:Staff Publications

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