Monday, August 13, 2012

Vaccines are available for some diseases but not others. How do vaccines work? Can researchers develop new vaccines for diseases like prostate cancer? 

Consider this example: When you get the measles vaccine, you receive multiple vaccinations to generate more immunological memory. Later in life, if you are exposed to the measles virus, your body will remember the benefits of the vaccine and protect you from the illness. 

This is how a prime-boost vaccination works to induce acquired immunity.  Such prime-boost vaccinations are the focus of Caitlin Lemke’s research as a postdoctoral scholar in the College of Pharmacy at the University of Iowa. 

Lemke has spent the last year-and-a-half testing a prime-boost vaccine for prostate cancer that targets Prostate Specific Antigen (PSA)—a protein produced by cells of the prostate gland. The PSA test measures the level of PSA in the blood. The higher a man’s PSA level, the more likely cancer is present. 

Lemke, an Iowa City native who earned her Ph.D. in immunology at the UI in 2006, is working with a heterologous prime-boost model—a model in which the first vaccination is different than the second. In contrast, when treated for measles, you receive the same vaccine each time. 

“Prime-boost vaccinations are really good at generating memory in our bodies' cells,” Lemke says. “With cancer, if you have a vaccine that can kill the existing tumors now, you want memory of immunity if there is a recurrence down the line.”   

Lemke’s prime-boost vaccination is a particle-based formulation made from a biodegradable polymer that breaks down into the human body’s normal metabolic by-products. “Cells acquire these by-products, become stimulated, and present the cancer-related antigen to T cells and other cells that will mount the anti-tumor response,” Lemke says. 

Her boost uses an adenovirus as the delivery vehicle. The adenovirus can be altered to carry genes that, when expressed, can produce proteins like PSA or any other desired model antigen. 

“When you receive the boost, a week after the prime vaccination, the stage has already been set; the cells are geared up and ready to go,” Lemke says. “You not only get a strong initial immune response, but you get really good memory of that immunity." 

“That’s what I am seeing and what other labs are seeing.” 

Lemke, who was awarded a prestigious 2009 Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation Postdoctoral Research Award, is testing these novel vaccines in mice. She is immunizing the mice weekly, drawing blood and analyzing the different immune cells, or antibodies, produced by the white blood cells. Lemke plans to tumor-challenge the mice to see how well the different treatment groups are protected 60 days after receiving the immunization. 

She is waiting 60 days as a test of cell memory. 

“I have other models where the mice are tumor challenged first,” Lemke says. “You give the mice a tumor and then you come in with your vaccine and see its effectiveness. I’ve gotten some interesting results, which have to be repeated to see how they hold up.” 

If these results are found to be reproducible, they will have significant implications in the design of vaccine dosage schemes for clinical trials. 

Lemke works in the laboratory of Aliasger Salem, an associate professor in the Department of Pharmaceutical Sciences and Experimental Therapeutics in the College of Pharmacy. The Salem Laboratory is collaborating with UI Urology Professor David Lubaroff, whose research group currently has a prostate cancer vaccine in clinical trials. Lemke is using Lubaroff’s one-dose adenovirus model in her studies. 

Lemke notes that researchers cure cancer in lab mice all the time. But curing cancer in humans is a completely different story.

The challenge won’t deter Lemke, whose tenacity helps her move forward with her research. 

“Caitlin is one of the hardest working, most perseverant and passionate postdoctoral fellows I have ever worked with,” Salem says. “When she comes across unexpected results, she will doggedly work at determining and understanding the mechanisms and pathways that led to those results. It’s this same enthusiasm and perseverance in her research that has resulted in these recent exciting results in her current prime-boost vaccination studies.” 

Lemke believes in mentoring graduate students, because not long ago she was one of them. 

“I always remember those first few weeks being a graduate student. I had no idea what was going on. More senior students took the time to show me how to do things and got me on my path,” Lemke says. “I remember how rewarding that was when it paid off and I gained my own independence. I enjoy the interaction with more junior students. I like their excitement. Maybe I can show them the enjoyment of being at the bench.”