Chapter 14: An Initial Translational Research Project: A Drug to Attack HER2-positive Breast Cancer

Chapter 14: An Initial Translational Research Project: A Drug to Attack HER2-positive Breast Cancer

Files

Loading...

Media is loading
 

Description

In this chapter, Dr. Hortobagyi talks about his first experience with translational research. He explains that while leading the Breast Cancer Research Group, he identified individuals with a collaborative mindset (Robert Bast, Gordon Mills, Mien Chie Hung [Oral History Interview]) and undertook translational research for the first time. They had success addressing resistance to chemotherapy with gene therapy, but the field progressed, and the results were not competitive. Combining forces with Mien Chie Hung, they then used the gene product E1-A to kill cells specific to HER2-positive breast cancer. The procedure worked, but they lacked resources to take the product to the drug phase.

Dr. Hortobagyi then explains that, at the time, individuals and institutions had little understanding about the legal issues attached to intellectual property and about raising money for development.

Dr. Hortobagyi explains that John Mendelsohn changed the Development Office and helped fund drug development. He also hired legal expertise so the intellectual property of individuals and the institution would be protected. Dr. Hortobagyi sketches the costs of drug development, noting that one can only develop a drug by partnering with industry and one “can’t do that without going to bed with the devil.”

Identifier

HortobagyiGN_02_20130107_C14

Publication Date

1-7-2013

Publisher

The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Administrator The Researcher Professional Practice The Professional at Work Collaborations On Research and Researchers On Pharmaceutical Companies and Industry Industry Partnerships Devices, Drugs, Procedures The Business of MD Anderson Portraits

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Gabriel Hortobagyi MD With that, then with those initial meetings I identified out of the 200-some people three or four individuals from the basic sciences who were really highly collaborative—so Mien-Chie Hung [Oral History Interview], Bob Bast, Gordon Mills, and later others—and with those, then we started to put together joint grant applications and joint papers and projects, and that became very, very exciting. And that’s when I started to get involved in true translational research, and that was the beginning of my interest in gene therapy. The first gene therapy program we got into was in the days of high-dose chemotherapy and bone marrow transplantation. Our first project—and this was before perfecting hematopoietic stem cell reinfusion, and therefore the abrogation of severe myelosuppression and potentially lethal myelosuppression—the idea was to take a mechanism of resistance to chemotherapy, and using gene therapy approaches, infect with that normal blood cell precursors so that while the cancer cells would be sensitive to chemotherapy, the blood cell precursors would be resistant. This was sort of the world upside down, we did that, and it was very exciting. And we transfected the P-glycoprotein into what today would be called probably hematopoietic stem cell, and then we infused that into patients before giving them high-dose chemotherapy. It worked beautifully in the lab. It worked beautifully in preclinical things, and we had some signal from our phase I trial that it might work some. But in the meantime, the field improved so much without that gene therapy that it became sort of an, okay. So what?

So, we said, “Well, we learned some things,” and of course, we did learn some things. Through the process we learned the difficulty of taking something that works very well in vitro or in a test tube and actually trying to deliver that product in vivo to a human being and making sure that it gets to the target cell and only to the target cell. Then we tried a number of delivery systems, and we did a lot of fairly sophisticated experiments that were very exciting. We got a number of publications out of that, so from the traditional academic point of view it was good. But it was five years of research that didn’t really move the field forward in the sense that we intended to move the field forward. Then we took what we learned from that experience, and then with Dr. Mien-Chie Hung, we developed a different gene therapy proposal, and that one was trying to use a gene product from adenovirus 5, which is called E1-A, to try to kill cells which we initially thought was specific to HER2-positive breast cancer, but it turned out it was not specific to that. That particular proposal we took all the way from the first concept in the lab to completing phase I and phase II studies, and it actually worked. But once we got there, we realized that neither we nor the institution had the resources to take this to a drug for FDA approval, so we looked for a partner in industry. We licensed it to a company. The company took the license, started to develop it, went bankrupt, and refused to give us back our license. So the thing is sitting in limbo somewhere, and it’s never going to make it beyond that.

Tacey Ann Rosolowski, PhD:



How frustrating!

Gabriel Hortobagyi, MD:

It is. Frustration is frequent in this field. In the meantime—

Tacey Ann Rosolowski, PhD:



Can I ask with the licensing issue, is that a place where contracts come in, if writing a contract differently would have protected you?

Gabriel Hortobagyi, MD:

Sure. If you go back even thirty years, I as an individual investigator and Mien-Chie Hung as another individual investigator and the institution as a whole had very primitive or no idea about the legal issues, the intellectual property issues, and the issues of how to obtain money for these things. Before Dr. [John] Mendelsohn was recruited, under Mickey [Charles A.] LeMaistre, we had a development office that essentially sat in the office and waited for checks to arrive. That was our fundraising effort. When Dr. Mendelsohn arrived, he essentially changed that on the model of Memorial Sloan-Kettering, which was already raising something like $100 million a year, and we developed what is today one of the most successful development offices in the world. And initially much of that went to support research. Today much of that goes to support bricks and mortar. At the same time, Dr. Mendelsohn recruited some legal expertise and developed the Technology Transfer Department, and we gradually learned how to deal with this. But when we started working on this, we had no idea about those complexities. We had no idea how malignant the environment is in the pharma world and how difficult it is for an inexperienced and rather naive investigator to try to survive.

We also had very little idea of how complicated and how costly it is to develop a drug and take it from concept to, “I'm going to sell it to the pharmacy.” Today it is considered that to do that pharma in general dedicates—it’s hard to tell exactly how much, because there is a lot of smoke and mirrors, and pharma adds a lot of other costs, including the cost of drugs that are never developed or that were unsuccessful. But they consider that to develop a new drug—take it from concept to a drug—takes anywhere from $2 billion to $4 billion. Between friends, that’s getting to be real money, and when you deal with the average size of an R01 being, I don't know, $250,000, it takes a lot to get even close to that. You cannot develop a drug by yourself. You can do it by partnering with the industry, but partnering with the industry is going to bed with the devil. You need to learn how to do that and not get burned.

Conditions Governing Access

Open

Chapter 14: An Initial Translational Research Project: A Drug to Attack HER2-positive Breast Cancer

Share

COinS