Cancer bags the second position on being the most lethal disease leading to fatality across the globe. According to WHO 1 in 10 Indians will develop cancer in course of their lifetime due to various factors. Identifying a marker for treating and eradicating cancer is the biggest challenge posed in front of the scientific community all over the world. There have been excellent strides in the invention of assessing and treating cancer which unquestionably is a life-threatening condition and a live terror to the diagnosed individuals. But what if we employ engineering techniques to cells of our esoteric living system and design a robust bioengineered weapon to fight back in the feud against cancer cells? It is possible through a fascinating branch of biology: Synthetic Biology. This brief article will explore further how bioengineered cells can help in the fight against cancer and recent developments in the field.

What Is Synthetic Biology?

  • Synthetic biology is identified as a “toolkit” which is biology-based and focusses to turn biology accessible to engineer. This branch of biology isn’t entirely brand new as a few characteristics feature of the branch find prominence in plant and animal breeding and genetic engineering where for more than decade genetic materials are amalgamated to a primary holy grail of new creation with desirable characteristic traits. Synthetic Biology is essentially the blueprint and establishment of new novel biological entities including genetic circuits, enzymes and redesigning already existing cells of biological entities.
  • The term synthetic biology has been used in several ways, for instance, to understand research combining principles of biology to design and modify pre-existing DNA and biology ultimately to produce a genetically modified entity with desirable features.
  • The differentiating factors between conventional genetic engineering and Synthetic biology lie in the fact that the latter aims to form a new blueprint of the genetic system and organisms using already present standardized parts. Synthetic biology also varies from customary molecular and cellular biology as it directs its focus on the design and construction of key ingredients like enzymes which can be modified to meet distinguish performance criteria.
  • In a nutshell Synthetic biologist design and construct biologically engineered cells which can be reprogrammed and modified to reveal and knockdown tumours just like how engineers with another major, plan circuits using materials with established tangible property to assemble a fully functional circuit and processors.

Tumor Immunology And Cancer Therapies

  • Cancer can affect all body tissues as they fool the highly regulated immune system by presenting a similar antigen to normal cells and under the immunosuppressive conditions, they are successful in halting cell division of normally functioning cells.
  • Cancer becomes a treacherous disease when a tumour starts to metastasize to other organs. Cancer cells are classified based on their cell type and tissue organization. Tumour belongs to a broad stretch of disease that emerges from under a differentiated mass of cells.
  • These tumours can be either benign and Malignant. Cancer immunology and research have been conducted across the globe over five decades yet there is no lasting cure as the molecular and cellular basis of Tumoral immunity continues to baffle the scientist.
  • But the understanding of the fundamental immune system and its regulation helps greatly to fabricate therapies to treat cancer.
  • By 2025 it is estimated that about 15.7lakh Indians would suffer from cancer following the increase in the incidence of cancer over decades. Decades of research on cancer immunology though didn’t find an ultimate cure for cancer yielded therapies that decreased the mortality rate in the previous decade.
  • Several predisposing factors determine the incidence of cancer. Few types of cancer are malignant and have the highest rate of mortality and serve as the reason for approximately 50% of cancer-related death. Cancer in the Lungs, breast, colorectal, prostate, bronchial, pancreatic, and ovary ranks high in the list.
  • The conventional therapies for treating cancer depends on the type and advancement of the tumour. Chemotherapy, Radiation therapy is the most common treatment method which employs drug and high rate of radiation to destroy and shrink the tumour cells and also exerts side effects.
  •  Hormonal therapy, Targeted therapy, Immunotherapy, Surgery, Stem cell transplant therapy are different other treatment methods devised for better treatment.

Immunotherapy

Synthetic Biology in Immunotherapy

Immunotherapy is recognized across the globe as the fourth cancer treatment method following radiation therapy, chemotherapy, and surgery. Significant research in understanding tumour immunology has paved a new treatment method with advanced clinical aid in combating tumour cells in the form of immunotherapy which serves its causes and affirms how the immune system works tirelessly to eradicate these menacing tumours cells.

It was Dr William Coley who conducted the first-ever immunotherapy for cancer by bacterial preparation to patients diagnosed with cancer in 1891, but it was only after the 1970s that Immunotherapy was actively employed in treating cancer. Currently, Cancer Immunotherapy has gained more significance as it opens to modern arenas and freshness to research to yield better treatment methods combined with another branch of science.

How Redesigning Biological Cells Can Aid in Combating Cancer?

Previously this article briefed about synthetic biology and Cancer immunotherapies further it is indispensable to know what transpires when bioengineering is employed to treat Cancer. This leads to the most fascinating ways how engineering biology (Synthetic biology) can be exploited in detecting and probably treating cancer.

Mothers Are Always Right

  • Eating greens might aid in maintaining good health but isn’t appetizing for many individuals. Dr Chun-Loong Ho and his colleagues from the Department of Biochemistry, National University Singapore (NUS) engineered bacteria making them even healthier.
  • Dr Chun Loong Ho his colleagues conducted a study in which they devised a way to produce a cocktail of vegetables and bacteria which when employed detects and destroys colorectal cancer cells.
  • Colorectal cancer remains one of the common cancers worldwide. The researchers with genetic techniques engineered familiar bacteria E. coli Nissle, a harmless bacteria found in the gut into a probiotic which can stick to colorectal cancer cells and release an enzyme that converts chemical substance found in cruciferous vegetables like broccoli ultimately serving as an anti-tumour agent.
  • The study successfully converted the food intake into a drug and killed 95% of colorectal cancer cells in a dish emphasizing the significant reduction of tumour size and potential method to halt tumour division and further prognosis. So next time when your mother asks you to eat green vegetables think twice before denying it.

Reviving Immune System Using Synthetic Gene Circuit

  • Tumour cells can evade and fool our highly regulated immune system and this factor serves as the prime reason why immunotherapy works effectively as they stimulate the immune system to destroy tumour cells.
  • Cancer cells differ from normal cells as they maintain a different profile of genomic expression. Studies conducted by Timothy Lu from Synthetic Biology Group of MIT Research Laboratory of Electronics engineered gene circuits that detect ovarian cancer cells.
  • They developed synthetic promoters which bind to a certain protein that is active in tumour cells to initiate gene expression specific to cancer cells. This circuit can be dispatched to cancerous cells using a virus.
  • The gene circuit installation paves a modern form of cancer immunotherapy. Mr Lu who headed the study points on how triggering the immune system appropriately will engage the regulated system to recognize tumour cells without checkpoint inhibitors.
  • This research idea gains the edge over existing immunotherapies as it can employ a more substantial number of markers thereby leading to distinct therapies.

Programmed Probiotics As Biosensor

  • Scientists from MIT and the University of California, San Diego followed the pioneer Dr William and found that bacteria can be used to recognize and treat cancer. Tal Danino one of the chief authors explained how they have programmed microbial probiotics to yield a molecule when it detects Tumor cells which can change the colour of urine.
  • As few bacteria can merrily survive in a tumour environment, engineering those bacteria to detect and eliminate will provide a new edge in treating cancer. Researches have employed Salmonella and Nissile 1917 which is present in yoghurt to serve as a biosensor that could recognize cancer in the liver which retains significance as other cancers like breast and colorectal cancer metastasize in the liver.
  • Other studies showed how Salmonella strains when engineered can secrete an anti-Tumor toxin into the cancer environment.
  • A Mice model study proved that the E.coli Nissle 1917 releases enzyme lacZ naturally in a Tumor environment in the liver and splits injected luciferin molecules from galactose.
  • Luciferin naturally when attached to sugar doesn’t glow but when the lacZ enzyme splits the sugar it glows and exits the biological system in urine thereby proving the uniqueness of this system over other approaches.

Subsequent Challenges And Conclusion

Immunotherapy has served effectively than radiation therapy and every day there is an experimental discovery that provides a better and enhanced perspective in understanding cancer and its treatment. Synthetic Biology enables advanced ways to treat cancer more precisely. All these approaches have been successful in an animal model (mice), but still, a  hypothesis for the human trail as it poses substantial challenges though there is progress in trials of these engineered therapies. This gives a hope that soon we will have a definite diagnosis and better treatment against the deadly disease To reword the Noble prize winner Malala Yousafzai’s speech:

‘ One lymphocyte, One antigen, One dendritic cell, One Engineered bacteria, One targeted therapy, and One drug can change the menacing cancer cells.’

Resources And Further Reading

https://theconversation.com/five-amazing-ways-redesigning-biological-cells-could-help-us-fight-cancer-95256

https://www.smithsonianmag.com/innovation/same-probiotic-thats-in-your-yogurt-could-detect-liver-cancer-180955491/

https://www.asme.org/topics-resources/content/bioengineering-may-key-cancer-fight

  • Immunotherapy of Cancer: An Innovative Treatment Comes of Age. (2016). Japan: Springer Japan.
  • Ho CL, Tan HQ, Chua KJ, Kang A, Lim KH, Ling KL, et al. Engineered commensal microbes for diet-mediated colorectalcancer chemoprevention. Nat Biomed Eng. Jan 2018.
  • Nissim, L., Wu, M. R., Pery, E., Binder-Nissim, A., Suzuki, H. I., Stupp, D., Wehrspaun, C., Tabach, Y., Sharp, P. A., & Lu, T. K. (2017). Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy. Cell171(5), 1138–1150.e15. https://doi.org/10.1016/j.cell.2017.09.049
  • Danino, T., Prindle, A., Kwong, G. A., Skalak, M., Li, H., Allen, K., Hasty, J., & Bhatia, S. N. (2015). Programmable probiotics for detection of cancer in urine. Science translational medicine7(289), 289ra84. https://doi.org/10.1126/scitranslmed.aaa3519
  • Chang, J. (2019). Bioengineering Innovative Solutions for Cancer. United Kingdom: Elsevier Science.
  • Balint, B., Pavlovic, M. (2015). Bioengineering and Cancer Stem Cell Concept. Germany: Springer International Publishing.
  • Ghassemi, M., Hashemi, M., Shahidian, A., Mohammadi, J. (2020). Bio-Engineering Approaches to Cancer Diagnosis and Treatment. Netherlands: Elsevier Science.