FC-optimized CD40 Agonist Antibodies can Induce a Persistent Anti-tumor Response
Bladder cancer is the tenth most common cancer in the world, In 2020, there will be an estimated 570,000 new cases of prostate cancer worldwide, most of which are men, accounting for 77%.
Most patients present with early non-muscular invasive bladder cancer (NMIBC). The current treatment strategy is to remove first and then BCG treatment. BCG treatment is to use live vaccines made of attenuated Mycobacterium bovis suspension for bladder perfusion, which can enhance the activity of macrophages and activate T lymphocytes. By enhancing the body's cellular immune function to cause anti-tumor response. However, up to 75% of patients do not respond to BCG treatment, and even if they do, there is a risk of recurrence and deterioration. Therefore, there is an urgent need to develop new therapies.
Recombinant human immunoglobulin G (IgG) antibodies can enhance the anti-tumor immune response. The stimulatory receptor CD40 plays a central role in the development of anti-tumor immunity and tumor-specific T cell responses.
The researchers found that the dendritic cells of bladder cancer highly express CD40, and the delivery of Fc-optimized CD40 agonistic antibodies into the bladder of tumor mouse models can promote the anti-bladder tumor response, indicating that this therapy has the potential to replace BCG in clinical bladder cancer treatment.
The antibody is composed of an antigen binding site (Fab) and a crystallizable site (Fc). Its Fab segment can recognize free molecular targets and receptors on the cell surface, which determines the specific recognition of the antibody to cancer cells, etc.; The Fc segment determines the effector function of the antibody, including antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). By optimizing and enhancing the Fc segment, the effector function of therapeutic antibodies can be improved.
The research team first used an orthotopic mouse model of bladder cancer to describe the tumor microenvironment and found that dendritic cells highly express CD40, indicating that CD40 plays an important role in bladder cancer tumors. Then tried to use CD40 antibody to antagonize CD40 in mouse tumors. Compared with BCG treatment, the CD40 antibody caused a significant reduction in bladder tumors.
CD40 antagonism can cause CD8+ T cell-dependent anti-tumor responses. Therefore, the research team used CD8 antibodies to deplete CD8+ T cells in mice and found that the anti-tumor effects of CD40 antibodies were greatly limited.
The research team used a fully human Fc-optimized anti-CD40 antibody to conduct experiments and found that its antagonism to CD40 in tumors induced humanized cells to produce powerful anti-tumor immunity.
The first-generation CD40 antibody has not been promoted due to its systemic toxicity. The research team evaluated the durability and side effects of human-derived Fc-optimized CD40 antibody and found that compared with BCG treatment, the intravesical delivery of human-derived Fc-optimized CD40 antibody was greatly reduced. The tumor volume has been decreasing continuously, and the mice did not show toxic reaction, indicating that the antibody has a good prospect for clinical application.
In summary, this study provides supporting evidence for the clinical transformation of bladder cancer treatment with CD40 agonistic antibodies, and determines an important mechanism by which CD40 drives the immune response of bladder cancer.
At present, Wuxi Donglin Sci & Tech Development Co.,Ltd. has developed a variety of Elisa products related to CD40L,If you want to know information about CD40L Elisa kits, you can directly visit the website:
http://www.dldevelop.com/uploadfile/data/DL-CD40L-b.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-c.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-Hu.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-Mu.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-p.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-Ra.pdf
Most patients present with early non-muscular invasive bladder cancer (NMIBC). The current treatment strategy is to remove first and then BCG treatment. BCG treatment is to use live vaccines made of attenuated Mycobacterium bovis suspension for bladder perfusion, which can enhance the activity of macrophages and activate T lymphocytes. By enhancing the body's cellular immune function to cause anti-tumor response. However, up to 75% of patients do not respond to BCG treatment, and even if they do, there is a risk of recurrence and deterioration. Therefore, there is an urgent need to develop new therapies.
Recombinant human immunoglobulin G (IgG) antibodies can enhance the anti-tumor immune response. The stimulatory receptor CD40 plays a central role in the development of anti-tumor immunity and tumor-specific T cell responses.
The researchers found that the dendritic cells of bladder cancer highly express CD40, and the delivery of Fc-optimized CD40 agonistic antibodies into the bladder of tumor mouse models can promote the anti-bladder tumor response, indicating that this therapy has the potential to replace BCG in clinical bladder cancer treatment.
The antibody is composed of an antigen binding site (Fab) and a crystallizable site (Fc). Its Fab segment can recognize free molecular targets and receptors on the cell surface, which determines the specific recognition of the antibody to cancer cells, etc.; The Fc segment determines the effector function of the antibody, including antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). By optimizing and enhancing the Fc segment, the effector function of therapeutic antibodies can be improved.
The research team first used an orthotopic mouse model of bladder cancer to describe the tumor microenvironment and found that dendritic cells highly express CD40, indicating that CD40 plays an important role in bladder cancer tumors. Then tried to use CD40 antibody to antagonize CD40 in mouse tumors. Compared with BCG treatment, the CD40 antibody caused a significant reduction in bladder tumors.
CD40 antagonism can cause CD8+ T cell-dependent anti-tumor responses. Therefore, the research team used CD8 antibodies to deplete CD8+ T cells in mice and found that the anti-tumor effects of CD40 antibodies were greatly limited.
The research team used a fully human Fc-optimized anti-CD40 antibody to conduct experiments and found that its antagonism to CD40 in tumors induced humanized cells to produce powerful anti-tumor immunity.
The first-generation CD40 antibody has not been promoted due to its systemic toxicity. The research team evaluated the durability and side effects of human-derived Fc-optimized CD40 antibody and found that compared with BCG treatment, the intravesical delivery of human-derived Fc-optimized CD40 antibody was greatly reduced. The tumor volume has been decreasing continuously, and the mice did not show toxic reaction, indicating that the antibody has a good prospect for clinical application.
In summary, this study provides supporting evidence for the clinical transformation of bladder cancer treatment with CD40 agonistic antibodies, and determines an important mechanism by which CD40 drives the immune response of bladder cancer.
At present, Wuxi Donglin Sci & Tech Development Co.,Ltd. has developed a variety of Elisa products related to CD40L,If you want to know information about CD40L Elisa kits, you can directly visit the website:
http://www.dldevelop.com/uploadfile/data/DL-CD40L-b.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-c.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-Hu.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-Mu.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-p.pdf
http://www.dldevelop.com/uploadfile/data/DL-CD40L-Ra.pdf
