Development of Plant Cell-Based Breast Cancer Antibody Treatment Production Technology
Aug 04, 2024
Domestic researchers have developed a plant cell line that produces antibodies for targeted therapy through gene scissors technology.
Antibodies produced in these plants have been shown to be similar in effect to commercialized breast cancer treatments, with less hepatotoxicity. This is expected to provide safe and effective treatment options for patients.
Professor Yoon Hye-won of the Department of Nuclear Medicine at Seoul National University Hospital, Professor Kim Sung-ryong of Sogang University, and a joint research team led by Shin Jun-hye, head of Pittomap's research institute, developed the world's first "PhytoRice" that removes all plant-specific glycan (carbohydrates that control function by attaching to proteins) that cause side effects of plant-derived antibodies, and announced the results of a study on the effectiveness of breast cancer antibody treatments produced based on this.
Approximately 20% of breast cancer patients are HER2-positive breast cancer in which HER2 receptors are abnormally overexpressed, and this type has rapid growth of cancer cells and is prone to recurrence and metastasis. HER2-targeted antibody treatments (such as trastzumab) treat HER2-positive breast cancer by blocking cancer cell proliferation signals or inducing cancer cells to become attack targets of immune cells.
These antibody treatments are mainly produced from animal cells, which are vulnerable to zoonotic diseases and have a high production cost because the process is difficult. As an alternative, plant-based antibody treatments, which are being actively studied, have been difficult to commercialize because they can cause immune side effects in humans.
Based on the fact that the immune side effects of plant-derived antibodies are caused by different sugar chain structures in humans and plants, the research team developed a rice cell line that removed all plant-specific sugar chains with gene scissors technology. After inserting the trastzumab (TMab) gene into this cell line to secrete antibodies, the secreted antibodies were cultured and purified to secure 'P-TMab (plant-producing breast cancer antibody)'.
As a result of analyzing the structure and component of the antibody, P-TMab had the same protein structure and cancer treatment mechanism as commercialized antibody treatment TMab.
As a result of analyzing the cell proliferation inhibitory effect on human breast cancer cells, it was found that P-TMab was more effective than TMab when the antibody concentration was 1 μg/ml or higher.
In addition, antibody-dependent cytotoxicity (ADCC) effect analysis was conducted to induce immune cells to attack cancer cells. As a result, P-TMab more than doubled the binding affinity of immune cells than TMab, resulting in greater apoptosis. This is because 'G0-type glycosyl' attached to P-TMab promoted binding to immune cells.
In fact, P-TMab showed the same apoptotic effect as TMab with less drug doses. (17ng/mL vs 54ng/mL)
Additionally, the team evaluated the hepatotoxicity of P-TMab and TMab. P-TMab decreased liver absorption from 6 h after administration and was rarely detected from 48 h, whereas TMab remained in the liver 48 h after administration. In other words, P-TMab has a lower risk of hepatotoxicity than conventional antibody treatments and can target tumors more efficiently instead of being absorbed less by the liver, the research team explained.
Professor Yoon Hye-won of the Department of Nuclear Medicine said, "This study confirms the possibility of treating cancer of plant-produced breast cancer antibodies, which is significant. The humanized plant cell line, which solves the immune side effects of plant-derived antibodies, is expected to be used in the development of new cancer drugs in the future as a platform for producing sustainable plant cell antibodies."
Meanwhile, the study was published online in the latest issue of the international journal 'Plant Biotechnology Journal (IF;10.1)'.
Antibodies produced in these plants have been shown to be similar in effect to commercialized breast cancer treatments, with less hepatotoxicity. This is expected to provide safe and effective treatment options for patients.
Professor Yoon Hye-won of the Department of Nuclear Medicine at Seoul National University Hospital, Professor Kim Sung-ryong of Sogang University, and a joint research team led by Shin Jun-hye, head of Pittomap's research institute, developed the world's first "PhytoRice" that removes all plant-specific glycan (carbohydrates that control function by attaching to proteins) that cause side effects of plant-derived antibodies, and announced the results of a study on the effectiveness of breast cancer antibody treatments produced based on this.
Approximately 20% of breast cancer patients are HER2-positive breast cancer in which HER2 receptors are abnormally overexpressed, and this type has rapid growth of cancer cells and is prone to recurrence and metastasis. HER2-targeted antibody treatments (such as trastzumab) treat HER2-positive breast cancer by blocking cancer cell proliferation signals or inducing cancer cells to become attack targets of immune cells.
These antibody treatments are mainly produced from animal cells, which are vulnerable to zoonotic diseases and have a high production cost because the process is difficult. As an alternative, plant-based antibody treatments, which are being actively studied, have been difficult to commercialize because they can cause immune side effects in humans.
Based on the fact that the immune side effects of plant-derived antibodies are caused by different sugar chain structures in humans and plants, the research team developed a rice cell line that removed all plant-specific sugar chains with gene scissors technology. After inserting the trastzumab (TMab) gene into this cell line to secrete antibodies, the secreted antibodies were cultured and purified to secure 'P-TMab (plant-producing breast cancer antibody)'.
As a result of analyzing the structure and component of the antibody, P-TMab had the same protein structure and cancer treatment mechanism as commercialized antibody treatment TMab.
As a result of analyzing the cell proliferation inhibitory effect on human breast cancer cells, it was found that P-TMab was more effective than TMab when the antibody concentration was 1 μg/ml or higher.
In addition, antibody-dependent cytotoxicity (ADCC) effect analysis was conducted to induce immune cells to attack cancer cells. As a result, P-TMab more than doubled the binding affinity of immune cells than TMab, resulting in greater apoptosis. This is because 'G0-type glycosyl' attached to P-TMab promoted binding to immune cells.
In fact, P-TMab showed the same apoptotic effect as TMab with less drug doses. (17ng/mL vs 54ng/mL)
Additionally, the team evaluated the hepatotoxicity of P-TMab and TMab. P-TMab decreased liver absorption from 6 h after administration and was rarely detected from 48 h, whereas TMab remained in the liver 48 h after administration. In other words, P-TMab has a lower risk of hepatotoxicity than conventional antibody treatments and can target tumors more efficiently instead of being absorbed less by the liver, the research team explained.
Professor Yoon Hye-won of the Department of Nuclear Medicine said, "This study confirms the possibility of treating cancer of plant-produced breast cancer antibodies, which is significant. The humanized plant cell line, which solves the immune side effects of plant-derived antibodies, is expected to be used in the development of new cancer drugs in the future as a platform for producing sustainable plant cell antibodies."
Meanwhile, the study was published online in the latest issue of the international journal 'Plant Biotechnology Journal (IF;10.1)'.
|
bellho@sportschosun.com
