Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice
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 pr...
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sg-ntu-dr.10356-984902023-02-28T17:04:38Z Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice 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. School of Biological Sciences DRNTU::Science::Biological sciences 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. Published version 2013-07-04T02:28:12Z 2019-12-06T19:55:58Z 2013-07-04T02:28:12Z 2019-12-06T19:55:58Z 2012 2012 Journal Article 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. 1949-2553 https://hdl.handle.net/10356/98490 http://hdl.handle.net/10220/10924 http://www.ncbi.nlm.nih.gov.ezlibproxy1.ntu.edu.sg/pmc/articles/PMC3326646/ en Oncotarget © 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: [http://www.ncbi.nlm.nih.gov.ezlibproxy1.ntu.edu.sg/pmc/articles/PMC3326646/]. 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. application/pdf |
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DRNTU::Science::Biological sciences 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. Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice |
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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. |
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School of Biological Sciences |
author_facet |
School of Biological Sciences 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. |
format |
Article |
author |
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. |
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Guo, Ke |
title |
Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice |
title_short |
Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice |
title_full |
Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice |
title_fullStr |
Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice |
title_full_unstemmed |
Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice |
title_sort |
engineering the first chimeric antibody in targeting intracellular prl-3 oncoprotein for cancer therapy in mice |
publishDate |
2013 |
url |
https://hdl.handle.net/10356/98490 http://hdl.handle.net/10220/10924 http://www.ncbi.nlm.nih.gov.ezlibproxy1.ntu.edu.sg/pmc/articles/PMC3326646/ |
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