Tag Archives: Genentech

Herceptin: When personalized medicine and animal research meet.

Personalized medicine is very popular among medical researchers these days, and it’s not hard to see why. By tailoring treatment to fit an individual patient, for example by using information about their genetic makeup, scientists hope to make treatments more effective while at the same time avoiding or minimizing adverse effects.

Anti-vivisectionist Dr. Greek writes about personalized medicine as if one could do this work without relying on animal research at all.

For example, he writes:

When will personalized medicine become a reality?

We are already seeing it, with breast cancer being a prime example. Breast cancer treatment is now determined in part based on a patient’s genetic makeup. About 25-30 percent of breast cancer patients overexpress the HER2 oncogene, which is a gene involved in the development of cancer. The overexpression results in an increase in the replication of the cancer cells. Physicians are now able to identify which breast cancer patients overexpress HER2 and give them Herceptin, a monoclonal antibody that inhibits HER2

This is true…  but where did Herceptin come from?   Does he know?

Herceptin, a humanized mouse monoclonal antibody. Image courtesy of Andrey Ryzhkov.

The basic research that led to the development of Herceptin (Trastuzumab) goes back to work by Milstein and Kohler who discovered the potential for using antibodies to fight disease.    They developed the first methods to produce monoclonal antibodies using mice.   Both Milstein and Kohler went on to win the Nobel Prize partly for this work.

Harold Varmus (now back as Director of the National Cancer Institute) showed that disturbances in some gene families could turn the cells cancerous.  He also went on to win the Nobel Prize for this work.  Robert Weinberg subsequently discovered in rats that a mutant gene (named “neu”) encoding a tyrosine kinase promoted cancer features in cells, contributing to the development of neuroglioblastoma tumors.

Later, Axel Ullrich and collaborators at Genentech cloned the human HER2/neu gene.  Work at UCLA Dennis Slamon and colleagues showed HER2 over-expression in 25% of patients with aggressive breast cancer.

Through screening studies on monoclonal antibody candidates in vivo in mice implanted with HER-2 positive human tumors the group at Genentech then developed the mouse 4D5 (parent of Herceptin) and showed that 4D5 could suppress the growth of HER2 tumor cells as well as enhance the ability of the host immune system to kill them.   A collaboration between UCLA and Genentech then demonstrated that radio-labeled 4D5 localized to HER2-expressing tumors in both mice and human patients.

With the information obtained from animal experiments, Genentech created Herceptin by humanizing the 4D5 mouse antibody directed at HER2.   The ability of Herceptin to prevent tumor growth was then assessed in mice implanted with HER-2 positive human tumor xenografts, and the concentration of Herceptin required in the blood to achieve anti-tumor activity was determined before starting human clinical trials.

So, you see…  Herceptin was derived from a mouse antibody.

Let me repeat: a mouse antibody!

Clinical trials in humans subsequently showed the effectiveness of Herceptin to treat HER2 positive breast cancer.

Perhaps, Dr. Greek and other animal rights activists should carefully listen to the experts that were actually involved in the process of developing Herceptin (a drug he appears to thinks highly of) which, indeed, benefits so many women battling breast cancer.   A drug derived from mice, and developed in mice.

Here is what Robert Weinberg had to say about Dr. Greek’s views on research:

Dr. Greek says the silliest things, […] implying that people are not studying human tumors, and implying that the kinds of experiments that one can do in mice can be done as well in humans — truly mindless!

I couldn’t have said it better.

Dario Ringach