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| ====== What are Synthetic Antibody Mimics (SyAMs)? ====== | ====== What are Synthetic Antibody Mimics (SyAMs)? ====== | ||
| - | Synthetic antibody mimics are synthetic organic molecules which are approximately one-twentieth the size of antibodies. These molecules have various advantages as they are composed of only 5 % of the molecular weight of natural antibodies, they are thermally stable (thus they are able to be stored at room structure) and can be orally administered. Other benefits include their inexpensive production and their limited adverse effects on the immune system. In essence, synthetic antibody mimics function by creating a link between target cells and immune cells to initiate a specific and targeted immune response (McEnaney, Fitzgerald, Zhang, Douglass, Shan, Balog, Kolesnikova & Spiegel, 2014). | + | Synthetic antibody mimics are synthetic organic molecules which are approximately one-twentieth the size of antibodies. These molecules have various advantages as they are composed of only 5 % of the molecular weight of natural antibodies, they are thermally stable (thus they are able to be stored at room structure) and can be orally administered. Other benefits include their inexpensive production and their limited adverse effects on the immune system. In essence, synthetic antibody mimics function by creating a link between target cells and immune cells to initiate a specific and targeted immune response (McEnaney et al., 2014). |
| ====== Fighting Against Disease ====== | ====== Fighting Against Disease ====== | ||
| - | ==== A Body's Natural Defenses ==== | + | ==== The Body's Natural Defenses ==== |
| The human body is generally quite effective in targeting and eliminating disease-causing agents (e.g. viruses & bacteria). It accomplishes this via its immune system which has two branches: Innate immune system and Adaptive immune system. The innate immune system is quite general and fights anything foreign in the body immediately. Examples of the innate immune system include physical barriers such as epithelial layers as well as chemical barriers such as mucosal layers and innate infection fighting cells such as macrophages (Parham, 2014). The adaptive immune system is more specific and takes some time to activate; however, it is responsible for clearing those pathogens that are able to evade the innate immune system and infect various cells within the human body. The adaptive immune system is heavily reliant on antibodies. These antibodies are produced by Plasma cells which are B-cells primed by dendritic cells upon contact of infectious pathogen in lymphatic system of the human body (Parham, 2014). | The human body is generally quite effective in targeting and eliminating disease-causing agents (e.g. viruses & bacteria). It accomplishes this via its immune system which has two branches: Innate immune system and Adaptive immune system. The innate immune system is quite general and fights anything foreign in the body immediately. Examples of the innate immune system include physical barriers such as epithelial layers as well as chemical barriers such as mucosal layers and innate infection fighting cells such as macrophages (Parham, 2014). The adaptive immune system is more specific and takes some time to activate; however, it is responsible for clearing those pathogens that are able to evade the innate immune system and infect various cells within the human body. The adaptive immune system is heavily reliant on antibodies. These antibodies are produced by Plasma cells which are B-cells primed by dendritic cells upon contact of infectious pathogen in lymphatic system of the human body (Parham, 2014). | ||
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| {{:figure_1.jpg|}} | {{:figure_1.jpg|}} | ||
| - | **Figure 2** <sup>[2]</sup>:This figure illustrates the interaction between a monoclonal antibody and an antigen on a cancer cell. Once the mAb attaches to the cancer cell it can recruit other immune cells (e.g. NK cells, macrophages etc.) to destroy the associated cancer cell. | + | **Figure 2**: This figure illustrates the interaction between a monoclonal antibody and an antigen on a cancer cell. Once the mAb attaches to the cancer cell it can recruit other immune cells (e.g. NK cells, macrophages etc.) to destroy the associated cancer cell (Burke, 2015). |
| As promising as the potential of mAbs sound, they have several disadvantages including life-threatening allergic responses, greater difficulty in the penetration of tissues due to their large composition and high mass as well as high production costs (Chames, Van Regenmortel, Weiss, & Baty, 2009). Consequently, David Spiegel and his colleagues generated a new class of organic molecules: Synthetic Antibody Mimics (SyAMs). This new type of molecule was discovered when trying to bring the target prostate cancer cell closer to immune cell to elicit an immune response (McEnaney et al., 2014). | As promising as the potential of mAbs sound, they have several disadvantages including life-threatening allergic responses, greater difficulty in the penetration of tissues due to their large composition and high mass as well as high production costs (Chames, Van Regenmortel, Weiss, & Baty, 2009). Consequently, David Spiegel and his colleagues generated a new class of organic molecules: Synthetic Antibody Mimics (SyAMs). This new type of molecule was discovered when trying to bring the target prostate cancer cell closer to immune cell to elicit an immune response (McEnaney et al., 2014). | ||
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| {{ http://i.dailymail.co.uk/i/pix/2015/02/10/2589AC7E00000578-0-The_synthetic_antibody_created_by_chemists_at_Yale_University_ca-a-5_1423573615755.jpg }} | {{ http://i.dailymail.co.uk/i/pix/2015/02/10/2589AC7E00000578-0-The_synthetic_antibody_created_by_chemists_at_Yale_University_ca-a-5_1423573615755.jpg }} | ||
| - | **Figure 3:**This figure depicts the ligand-receptor binding nature of the SyAM-P molecule (McEnaney et al., 2014). | + | **Figure 3:**This figure depicts the ligand-receptor binding nature of the SyAM-P molecule (Gray, 2015). |
| ====== Synthesis & Effector Function of SyAM-Ps ====== | ====== Synthesis & Effector Function of SyAM-Ps ====== | ||
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| {{:crystallized_structure_of_fcgammar1.png|}} | {{:crystallized_structure_of_fcgammar1.png|}} | ||
| + | |||
| **Figure 5**: Shows the crystallized structure of FcγRI (McEnaney et al., 2014). | **Figure 5**: Shows the crystallized structure of FcγRI (McEnaney et al., 2014). | ||
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| ====== Future Applications ====== | ====== Future Applications ====== | ||
| - | Beyond its potential for treating prostate cancer, SyAms may have applications for treating other forms of cancer, and various bacterial and viral diseases<sup>[7]</sup>.<sup>[3]</sup> The ability to do so is possible by controlling the framework and properties of the antibody and by creating the optimal characteristics for the binding of some protein to receptor on the cancer or bacteria / virus<sup>[8]</sup>. In-vitro construction of the SyAMs would allow the creation of accurately engineered binding specific proteins, which would ultimately cause the body to trigger a natural immune response via the created SyAM (Brigandi, 2016). | + | Beyond its potential for treating prostate cancer, SyAms may have applications for treating other forms of cancer, and various bacterial and viral diseases. The ability to do so is possible by controlling the framework and properties of the antibody and by creating the optimal characteristics for the binding of some protein to receptor on the cancer or bacteria / virus. In-vitro construction of the SyAMs would allow the creation of accurately engineered binding specific proteins, which would ultimately cause the body to trigger a natural immune response via the created SyAM (Brigandi, 2016). |
| Moreover, SyAms are becoming more popular due to the fact that they are less likely to instigate an adverse immune response because of their small molecular mass, high specificity and thermal stability (McEnaney et al., 2014). The fact that antibodies are proteins makes them generally more challenging to produce (Sharpe & Freeman, 2002), and even when one is able to manufacture them, proteins denature over time - another disadvantage (Davis, 2005). On the other hand, SyAms are made of peptides instead of proteins, making them more resistant to denaturing. Additionally, SyAms are cheaper and easier to produce than antibodies (McEnaney et al., 2014). Patients would be able to take the SyAms orally like conventional drugs (McEnaney et al., 2014), which results in a more efficient immune response, viable because of their compact size. This can be vastly advantageous to patients with cancers and autoimmune diseases, like multiple sclerosis in which patients undergo maddening, monoclonal antibody therapies. Additionally, the small size of the antibody mimics can be used as an asset to eliminate tumors. Although SyAms are currently in the beginning stages, the efforts made by the immunologists and bioengineers show SyAms will have the potential for treating a broad range of bacterial diseases and other complications. | Moreover, SyAms are becoming more popular due to the fact that they are less likely to instigate an adverse immune response because of their small molecular mass, high specificity and thermal stability (McEnaney et al., 2014). The fact that antibodies are proteins makes them generally more challenging to produce (Sharpe & Freeman, 2002), and even when one is able to manufacture them, proteins denature over time - another disadvantage (Davis, 2005). On the other hand, SyAms are made of peptides instead of proteins, making them more resistant to denaturing. Additionally, SyAms are cheaper and easier to produce than antibodies (McEnaney et al., 2014). Patients would be able to take the SyAms orally like conventional drugs (McEnaney et al., 2014), which results in a more efficient immune response, viable because of their compact size. This can be vastly advantageous to patients with cancers and autoimmune diseases, like multiple sclerosis in which patients undergo maddening, monoclonal antibody therapies. Additionally, the small size of the antibody mimics can be used as an asset to eliminate tumors. Although SyAms are currently in the beginning stages, the efforts made by the immunologists and bioengineers show SyAms will have the potential for treating a broad range of bacterial diseases and other complications. | ||
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| ====== References ====== | ====== References ====== | ||
| - | [1] Bracci, L., Schiavoni, G., Sistigu, A., & Belardelli, F. (2014). Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. Cell Death & Differentiation, 21(1), 15-25. | + | [1] Bracci, L., Schiavoni, G., Sistigu, A., & Belardelli, F. (2014). Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. //Cell Death & Differentiation//, 21(1), 15-25. |
| [2] Brigandi, R. (n.d.). The development of synthetic antibody mimics to improve immunotherapy methods. Retrieved January 26, 2016, from http://www.pitt.edu/~rpb38/wassignment2.html | [2] Brigandi, R. (n.d.). The development of synthetic antibody mimics to improve immunotherapy methods. Retrieved January 26, 2016, from http://www.pitt.edu/~rpb38/wassignment2.html | ||
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| [3] Burke, J. (2015, September 14). Multiple Melanoma: The Antibodies are Coming!. Retrieved from http://www.rockymountaincancercenters.com/wp-content/uploads/2015/08/Monoclonal-antibody1.jpg | [3] Burke, J. (2015, September 14). Multiple Melanoma: The Antibodies are Coming!. Retrieved from http://www.rockymountaincancercenters.com/wp-content/uploads/2015/08/Monoclonal-antibody1.jpg | ||
| - | [4] Chames, P., Van Regenmortel, M., Weiss, E., & Baty, D. (2009). Therapeutic antibodies: successes, limitations and hopes for the future. British journal of pharmacology, 157(2), 220-233. | + | [4] Chames, P., Van Regenmortel, M., Weiss, E., & Baty, D. (2009). Therapeutic antibodies: successes, limitations and hopes for the future. //British journal of pharmacology//, 157(2), 220-233. |
| [5] Chu, A. (2014). Immune System Defenses. 5-9. | [5] Chu, A. (2014). Immune System Defenses. 5-9. | ||
| - | [6] Davis, M.I. (2005). Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. RCSB PDB. 102, 5981-5986. | + | [6] Davis, M.I. (2005). Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. //RCSB PDB//. 102, 5981-5986. |
| [7] Government of Canada. (2001). How Drugs are reviewed in Canada [fact sheet]. Retrieved from: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/activit/fs-fi/reviewfs_examenfd- eng.php | [7] Government of Canada. (2001). How Drugs are reviewed in Canada [fact sheet]. Retrieved from: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/activit/fs-fi/reviewfs_examenfd- eng.php | ||
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| [8] Gray, R. (2015). An immune system in a pill? First synthetic antibodies created that could one day treat cancer and even HIV. Science and Tech. | [8] Gray, R. (2015). An immune system in a pill? First synthetic antibodies created that could one day treat cancer and even HIV. Science and Tech. | ||
| - | [9] Klein, J.S., Gnanapragasam, P. N. P., Galimidi, R. P., Foglesong, C. P., West, A. P., & Bjorkman, P.J. (2008). Examination of the contributions of size and avidity to the neutralization mechanisms of the anti-HIV antibodies b12 and 4E10. Proceedings of the National Academy of Sciences, 106, 7385-7390. | + | [9] Klein, J.S., Gnanapragasam, P. N. P., Galimidi, R. P., Foglesong, C. P., West, A. P., & Bjorkman, P.J. (2008). Examination of the contributions of size and avidity to the neutralization mechanisms of the anti-HIV antibodies b12 and 4E10. //Proceedings of the National Academy of Sciences//, 106, 7385-7390. |
| - | [10] McEnaney, P. J., Fitzgerald, K. J., Zhang, A. X., Douglass Jr, E. F., Shan, W., Balog, A., … & Spiegel, D. A. (2014). Chemically Synthesized Molecules with the Targeting and Effector Functions of Antibodies. Journal of the American Chemical Society, 136(52), 18034-18043. | + | [10] McEnaney, P. J., Fitzgerald, K. J., Zhang, A. X., Douglass Jr, E. F., Shan, W., Balog, A., … & Spiegel, D. A. (2014). Chemically Synthesized Molecules with the Targeting and Effector Functions of Antibodies. //Journal of the American Chemical Society//, 136(52), 18034-18043. |
| [11] Parham, P. (2014).The immune system. Garland Science. | [11] Parham, P. (2014).The immune system. Garland Science. | ||
| - | [12] Sharpe, A.H. and Freeman, G.J. (2002). The B7-CD28 Superfamily. Nature Reviews Immunology, 2, 116-126. | + | [12] Sharpe, A.H. and Freeman, G.J. (2002). The B7-CD28 Superfamily. //Nature Reviews Immunology//, 2, 116-126. |
| [13] Shelton, J. (2014). New class of synthetic molecules mimics antibodies. Yale News. Retrieved January 29, 2016, from http://news.yale.edu/2014/12/17/new-class-synthetic-molecules-mimics-antibodies | [13] Shelton, J. (2014). New class of synthetic molecules mimics antibodies. Yale News. Retrieved January 29, 2016, from http://news.yale.edu/2014/12/17/new-class-synthetic-molecules-mimics-antibodies | ||
| - | [14] Weiner, L. M., Surana, R., & Wang, S. (2010). Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nature Reviews Immunology,10(5), 317-327. | + | [14] Weiner, L. M., Surana, R., & Wang, S. (2010). Monoclonal antibodies: versatile platforms for cancer immunotherapy.// Nature Reviews Immunology//,10(5), 317-327. |
| - | [15] Wine, Y. (2013). Molecular deconvolution of the monoclonal antibodies that comprise the polyclonal serum response. PNAS, 110(8), 2993-2998. | + | [15] Wine, Y. (2013). Molecular deconvolution of the monoclonal antibodies that comprise the polyclonal serum response. //PNAS//, 110(8), 2993-2998. |
