2013 Sean Patrick Recipients
2013 Sean Patrick Recipients

2013 Recipients of the Sean Patrick Multidisciplinary Collaborative Grant

HERA awarded the 2013 Sean Patrick Multidisciplinary Collaborative Grant to Dr. Daniel Vallera and Dr. Daniel Kaufman from the University of Minnesota.  Their exciting research, “Recruiting the Immune System to Attack Ovarian Cancer,” targets ovarian cancer stem cells using the Natural Killers cells of the immune system to destroy ovarian cancer.  Following is a Q & A describing their collaborative project.

Dr. Daniel Vallera

Q:  What is the primary goal of your HERA-funded study?

The primary goal is to develop a new drug that targets ovarian cancer stem cells. These are the cells responsible for drug resistance. More specifically, the Natural Killer (NK) cells of the immune system carry packets of toxins and enzymes that kill their targets. So, by specifically targeting them to ovarian cancer stem cells, Dr. Daniel Vallera has developed a natural means of selectively destroying ovarian cancer. Therefore, the idea is that once cancer has become drug resistant, attack the cancer stem cells that are the root cause of the resistance. This is accomplished using an artificially-constructed bispecific antibody whereby one part of it binds to ovarian cancer stem cells, the other part binds to  NK cells. This locks the NK cell and cancer cell in close proximity so that the NK cell can better kill its target.  If there is not enough of these NK cells present, Dr. Kaufman has developed a way of genetically deriving armies of NK cells from normal (non-cancerous) stem cells. Dr. Melissa Geller is a prominent ovarian cancer clinician and scientist.  Her job will be to provide primary tumors from patients to test our new drug.

Q:  Your team has developed a drug that targets cancer stem cells.  How are cancer stem cells different from other ovarian cancer cells?

Ovarian cancer stem cells represent a smaller portion (5-15%) of the ovarian cancer cell population. However, it is these cells that are most resistant to chemotherapeutic drugs and responsible for drug refractory relapse.  We have data in a mouse model that shows that if this minority population of human cancer stem cells are eliminated, then ovarian tumors will regress. The antibody that we are using to specifically target cancer stem cells has certain unique characteristics; this antibody has been the focus of Dr. Vallera’s research for the past year.

Dr. Daniel Kaufman

Q:  What are Natural Killer cells?  Why are they important in the progression of ovarian cancer? How will they be targeted in your study?

Natural killer are the white blood cells that are part of our innate immune system. They patrol and eliminate cellular invaders such as ovarian cancer cells. When tumors get established they are not as effective because they have no means to recognize them specifically. They also carry a somewhat unique fingerprint on their surface called CD16. We have genetically engineered an antibody fragment that binds to CD16 on NK cells and can be used to make our bispecific drug.

Q:  Why is your proposed immunotherapy-based ovarian cancer treatment better than traditional chemotherapy treatments?

As we all know, the most serious ovarian cancer cases are the the cases that relapse after traditional chemotherapy treatment. Those drugs are then worthless for therapy and sometimes it is difficult or impossible to find alternative treatments. This type of drug harnesses the power of your own immune system, so that the immune cells which frequently have a hard time finding their way to the tumor has a means of coupling to the tumor to enhance their effectiveness. They kill the cancer cells by a mechanism entirely unrelated to the mechanism of killing used by tradition chemotherapy treatment.

Q:  What are the biggest challenges – or obstacles – of this proposed work?

Preliminary studies show that the drug works very well and does what it is supposed to do. The biggest challenges will be developing a meaningful animal model and scaling up to produce large amounts of drug and NK cells for a clinical trial.

Q:  Have you collaborated together before?  What made you want to work together on this project?  Explain why forming this team will be key to your success.

We have only begun to work together. Since the drugs Dr. Vallera makes target NK cells and Dr. Kaufman has a new way of producing stem cell derived NK cells, the collaboration seemed natural. The team will be a great key to success since Dr. Vallera has the knowledge and experience of biological drug production and Dr. Kaufman is a stem cell/NK cell expert.

Q:  Do you think we are close to a cure for ovarian cancer?

The cure for ovarian cancer will not occur overnight. But we believe that with all of the new scientific technical advances we are on the threshold of new advances that will significantly affect the cure rate. We believe the next major advance will occur in ovarian cancer. Two reasons are that this type of drug targets ovarian cancer stem cells, the root of drug resistance and the drug can be given intraperitoneally which may be a way to get more drug delivered directly to the site of the cancer.

Click here to read about the 2011 Sean Patrick Multidisciplinary Collaborative Grant recipients.

Click here to read about the 2012 Sean Patrick Multidisciplinary Collaborative Grant recipients.

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