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Title: Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice
Authors: Guo, Ke
Tang, Jing Ping
Jie, Li
Hong, Cheng William
Tan, Cheng Peow Bobby
Park, Jung Eun
Varghese, Leyon
Feng, Zhiwei
Zhou, Jianbiao
Chng, Wee Joo
Zeng, Qi
Al-Aidaroos, Abdul Qader O.
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2012
Source: Guo, K., Tang, J. P., Jie, L., Al-Aidaroos, A. Q. O., Hong, C. W., Tan, C. P. B., et al. (2012). Engineering the First Chimeric Antibody in Targeting Intracellular PRL-3 Oncoprotein for Cancer Therapy in Mice. Oncotarget, 3(2), 158-171.
Series/Report no.: Oncotarget
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.
ISSN: 1949-2553
Rights: © 2012 The Authors. This paper was published in Oncotarget and is made available as an electronic reprint (preprint) with permission of The Authors. The paper can be found at the following official open URL: []. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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