20.109:Module 4 Research Proposal
We propose a novel method of delivering pharmacological agents, such as chemotherapeutic compounds, to cancer cells through specific targeting by an adenovirus. We aim to functionalize viruses with antibodies or other targeting methods such that they specifically infect cancer cells and deliver the attached pharmacological cargo.
- Cancer is one of the leading causes of death throughout the world.
- A major obstacle is cancer treatment is the lack of specificity - drugs attack cancerous cells, but they attack healthy cells as well
- Tumor cells over-express certain cell surface receptors, and many antibodies have been developed against a wide array of these receptors (e.g. CD25 in T cell lymphoma and CD22 in B cell lymphoma)
- Huge variety - can infect all living things
Research Problem and Goals
Project Details and Methods
Linking drug to virus
Modifying specificity of virus
If all goes well, our virus should be able to deliver cancer drugs specifically to cancerous cells.
- Yacoby, I, et al. "Targeting antibacterial agents by using drug-carrying filamentous bacteriophages." Antimicrobial Agents and Chemotherapy 50.6(June 2006): 2087-2097.
This study used a method similar to our proposal, but with modified bacteriophages delivering antibiotics to target bacteria.
- Jung J, et al. "Bio-nanocapsules for In vivo Pinpoint Drug Delivery." Yakugaku Zasshi 127.5(May 2007): 797-805.
This study uses a recombinant yeast-derived hepatitis B virus surface antigen particle as a hepatitis B vaccine, but the particle can incorporate other types of materials as well.
- Lu, S, et al. "Gene Therapy for Ovarian Cancer Using Adenovirus-Mediated Transfer of Cytosine Deaminase Gene and Uracil Phosphoribosyltransferase Gene Directed by MDR1 Promoter." Cancer Biology Therapy 6.3(March 2007).
This study used an adenovirus to deliver gene therapy to ovarian cancer cells. While we wish to use drug treatment instead, this virus as a vector for delivery is promising.
- Maatta, A. M., et al. "Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models." International Journal of Cancer."
This study examined the success of utilizing the Semliki Forest Virus to treat mouse tumor models. The results were very good, as tumor growth rate drastically decreased.