Proof of Concept

Overview

Introduction


Cervical cancer is the fourth most notorious cancer that has affected women globally. Despite being preventable through vaccine and pap smear screening, the low rate of prevention and early detection contributes to the high mortality effect of cervical cancer. Ninety percent of cases are attributed to low-middle income countries. [1] Researchers worldwide try to develop effective drugs to cure cervix cancer, however this effort comes to no avail as lots of predicaments appear, even with the most sophisticated technology. Lots of side effects emerge that worsen cancer patient quality of life.[2,3] Not to mention, drug resistance during regimen treatment also becomes more common nowaday.[4]


Therefore, we, CERVEX, aim to produce more effective cervical cancer treatment by utilizing non-pathogenic Salmonella Typhimurium. This bacteria will be modified into A1-R strain to further escalate the specificity in detecting cancer cell, along with its efficiency to eradicate it at the same time. We plan to incorporate a broad anti cancer drug (buforin iib) within this strain, along with p53 sensor to ensure that the drug is delivered in the most appropriate time, which is within the cancer microbiological environment.

Safety protocol


We strictly adhere to BSL 2 precautions and Virology and Cancer Pathobiology Research Center standard of procedure. By using 3 rooms with different contamination levels, we ensure no contamination comes out from one lab to the others. Our wet lab members have undergone biosafety training, and wear proper PPE during experiment, including coverall hazmat, nitrile glove, mask, and shoe cover. In BSL 1 setting, we also use lab coats, nitrile gloves, and masks. All of our protocols have been reviewed by the head of Virology and Cancer Pathobiology Research Center, Ms. Aroem Naroeni, DEA, PhD, and the whole experiments are under supervision by laboratory assistants

Why salmonella


Salmonella has many upper hand compared to other biological vectors, including: [5,6]


  • High safety profile (able to target cancer cell 1000x more specific than healthy cell)
  • Able to distribute and penetrate tumor optimally due to its flagella
  • High affinity toward antigen presenting cell (APC), able to stimulate the immune system, particularly T cell CD8+
  • Able to induce apoptosis due to its natural toxicity
  • Downregulate tumor chemotherapeutic resistance
  • Able to survive in the tumor hypoxia microenvironment
  • Induce cancer cell cycle that initially remains in G0/G1 into S/G2/M, thus allowing cancer cell to be sensitive to the chemotherapeutic effect

The upper hand of salmonella modification to A1-R


  • Higher specificity toward cancer cell further than VNP20009, strain that has successfully entered first human trial in curing cancer, hence better safety profile
  • Has more toxic property compared to VNP20009, hence increasing the efficacy of tumor eradication
References
  1. https://www.who.int/news-room/fact-sheets/detail/cervical-cancer
  2. https://pubmed.ncbi.nlm.nih.gov/27509935/
  3. https://pubmed.ncbi.nlm.nih.gov/32321767/
  4. https://www.sciencedirect.com/science/article/pii/S266739402200048X
  5. https://www.hindawi.com/journals/jir/2018/2984247/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957602/
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657113/
  8. Dos Santos, A. M. P., Ferrari, R. G., & Conte-Junior, C. A. (2018). Virulence Factors in Salmonella Typhimurium: The Sagacity of a Bacterium. Current Microbiology. doi:10.1007/s00284-018-1510-4
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775532/#:~:text=Among%20bacteria%20used%20for%20cancer,and%20its%20natural%20toxicity%2061.
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064865/
  11. https://biosafety.wsu.edu/hela-cell-lines/#:~:text=HeLa%20cell%20lines%20were%20derived,for%20most%20HPV-caused%20cancers
  12. https://sci-hub.se/10.1158/0008-5472.CAN-06-0716