Researchers in Denmark have used the malarial protein VAR2CSA to kill selectively cancer cells. Malarial parasites are known to attack the placenta. The researchers, while studying how to protect the placenta from malarial parasites, accidentally stumbled upon a potential cure for cancer.

The following is the sequence of scientific events that led to this serendipitous discovery:

1. The scientific community knew that placental cells and the majority of cancerous cells express a distinct type of chondroitin sulfate on their surface.
   
2. The research team of the current study, led by Ali Salanti and Mads Daugaard, found that the malarial parasite uses the VAR2CSA, a transmembrane protein, to attach to the chondroitin sulfate on the surface of the placental cells, leading to infection and consequent killing of placental cells by malarial parasites.
   
3. After deciphering the mechanism of infection of placental cells by malarial parasites, the researchers hypothesized that the malarial parasite protein VAR2CSA should also attach to chondroitin sulfate on cancerous cells.
   
4. The hypothesis was proven correct when the scientists demonstrated that the parasite protein VAR2CSA indeed attaches to cancerous cells.
   
5. Next, the researchers attached Diphtheria toxin to VAR2CSA by recombinant protein technology and injected this recombinant protein into mice with cancer.
   
6. The recombinant VAR2CSA-Diphtheria toxin attached itself to the cancerous cells while sparing normal cells, thus selectively directing the deadly Diphtheria toxin to the cancerous cells, leading to the killing of cancerous cells in mice.
   
7. Thus, scientists were successful in utilizing the similarity between the surface sugar molecules in the placenta and cancer cells to design a treatment that selectively killed cancerous cells.

Having succeeded in curing cancer in mice by injecting them with recombinant malarial protein VAR2CSA attached with Diphtheria toxin, the research team is planning to try this novel therapy in human subjects.  

Written by Dr. Ashish Patil

Primary Reference           

Ali, S., Clausen, T., Agarbaek, M., Nakouzi, N., Dahlback, M., Oo, H., . . . Daugaard, M. (2015). Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein. Cancer Cell, 28(4), 500-514.

Additional References

Sinderen, M., Cuman, C., Winship, A., Menkhorst, E., & Dimitriadis, E. (2013). The chrondroitin sulfate proteoglycan (CSPG4) regulates human trophoblast function. Placenta, 34(10), 907-912.

Salanti, A., Dahlback, M., Turner, L., Nielson, M., Barfod, L., Magistrado, P., . . . Theander, T. (2004). Evidence for the Involvement of VAR2CSA in Pregnancy-associated Malaria. Journal of Experimental Medicine, 200(9), 1197-1203.