Herceptin

In 1986, Alex Ullrich, a scientist working for the biomedical company Genentech, discovered a protein that was created by the Her2 gene. Her2 is considered an oncogene that causes cancer to develop and grow, and the Her2 gene belongs to a family of genes that stimulates cell growth.

In 1998, scientists found that Her2 gene and protein were associated with adverse breast cancer. Doctors began measuring Her2 protein levels in breast tumors and using this information to determine a prognosis and whether a patient required chemotherapy. The Her2 gene was considered active, or what doctors call over-expressed, in approximately 20-25% of breast cancers.

Trastuzumab (sold under the brand name Herceptin®), the first monoclonal antibody that fights against breast cancer, was developed with mice. It was developed by the company Genentech. The B-cells in mouse spleen produce antibodies after they are injected with pathogens, and they fuse with human myeloma cells to form hybridoma cells that have longer lifespan. The process of the formation of monoclonal antibodies is illustrated by figure 1.

Figure 1

Source: Alpha Lifetech

The HER2 genes produced by some breast cancer cells make HER2 receptors that receive signals that stimulate the cell to grow and multiply on the surface of all cells. When the cancer cells overexpress the HER2 genes, more HER2 receptors receive growth signals. Trastuzumab attach itself to the HER2 receptors and block the growth signals in order to slow and stop the replication of breast cancer cells. In addition, it helps alert the immune system to destroy the cells it attached. Figure 2 demonstrates the mechanism of Herceptin.

As a result, 6 months of Herceptin treatment cured 89.4% breast cancer patients.

Figure 2

Source: Herceptin

Monoclonal antibodies are laboratory-produced proteins (antibodies) that can bind to only one antigen. There are also other types of antibodies, such as polyclonal antibodies, which bind to multiple antigens.

"The monoclonal antibody is the closest we have come to the 'magic bullet', and this relatively new class of medicine is having a major impact in treating hitherto untreatable conditions." Les Iversen once wrote in his book.

Moreover, the market for therapeutic antibody drugs has experienced explosive growth. Graph below is the timeline from 1975 showing the successful development of therapeutic antibodies and their applications.

Figure 3

Source: BMC

1. American Cancer Society, “Targeted Drug Therapy for Breast Cancer”. Accessed at https://www.cancer.org/cancer/breast-cancer/treatment/targeted-therapy-for-breast-cancer.html

2. Ian Le Guillou, UAR news team, Herceptin - first monoclonal antibody treatment for cancer, Understanding Animal Research, 2014. Accessed at https:// www.understandinganimalresearch.org.uk/news/communications-media/herceptin-first- monoclonal-antibody-treatment-for-cancer/

3. Breastcancer.org, Herceptin, 2020. Accessed at https://www.breastcancer.org/treatment/ targeted_therapies/herceptin#top

4. Breastcancer.org, Early Results Suggest 6 Months of Herceptin as Effective as Treatment for 1 Year, 2019. Accessed at https://www.breastcancer.org/research-news/herceptin-for-6-months- seems-same-as-1-yr

5. https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art-20047808

6. https://www.medicinenet.com/monoclonal_antibodies/article.htm#what_are_human_monoclonal_antibodies​

7. Les Iversen, Drugs: A Very Short Introduction, New York: Oxford University Press, 2016, pp.103-105

8. Lu, RM., Hwang, YC., Liu, IJ. et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci 27, 1 (2020). https://doi.org/10.1186/s12929-019-0592-z

9. https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0592-z#Abs1

10. https://www.breastcenter.com/2020/03/04/a-brief-history-of-herceptin-and-the-her2-cancer-gene/