The Promise of Vaccine Therapy

Patients are beginning to reap the rewards of preventive and therapeutic cancer vaccines.

Vaccines boost our immune system’s ability to defend against disease, but harnessing this defense mechanism in the war against cancer has eluded investigators for years. Now an increasing number of vaccine therapies are producing promising results against various cancers.

There are currently more than 900 cancer vaccine studies listed on the National Institutes of Health’s registry of clinical trials.1 These studies are being conducted by researchers in the United States and abroad who are working to prevent and treat cancer.2

Worthy of note are the vaccines that have already been approved by the U.S. Food and Drug Administration (FDA) for the prevention of cancer: Gardasil® (Quadrivalent Human Papillomavirus [types 6, 11, 16, 18] Recombinant Vaccine) and Cervarix® (Bivalent Human Papillomavirus [types 16 and 18] Recombinant Vaccine), both of which target high-risk types of human papillomavirus (HPV) that can cause cervical cancer; and the hepatitis B vaccine, approved in 1981 for the prevention of hepatitis B infections, which can lead to primary liver cancer.

The newest addition to the toolbox of cancer weaponry is Provenge® (sipuleucel-T)—the first therapeutic vaccine for fighting existing malignancies. Provenge won FDA approval in April 2010 for treating advanced prostate cancer.

How Do Cancer Vaccines Work?

Vaccine therapy works by generating a response from the cells in the immune system against specific antigens, or foreign bodies. When the cells in the immune system recognize the antigen, they multiply to fight it off.

Today’s preventive cancer vaccines, like Gardasil, protect against viruses like HPV, known to be co-factors for various cancers. By preventing viral infections, these vaccines keep specific cancers from occurring in the vaccinated population.

With therapeutic cancer vaccines, the antigens themselves are harvested from the patient’s own cancer cells, or they are produced in a lab with stem cells, ensuring that the vaccine targets only those specific cells and not healthy cells. Because vaccine therapies target only cancer cells, these therapies do not produce the side effects that accompany chemotherapy and radiation treatments.

“By harnessing the power of the patient’s own immune cells, we are able to avoid the side effects brought on by radiation and chemotherapy, which sometimes can be as devastating as cancer itself,” says Johannes Vieweg, MD, chair and professor, University of Florida, Department of Urology.

Vaccines in the Pipeline

Recent vaccine research is showing promising results. Dr. Vieweg’s cancer immunotherapy research is concerned with patients with prostate cancer and advanced renal cell carcinoma (the most common type of kidney cancer). He has developed two cell-based vaccines aimed at “recognizing” the tumor from which the cells were originally harvested. Vaccines are tagged with a small molecule from the surface of the cancer cell and are then injected back into the patient, where, upon reaching the lymph nodes, the surface molecules act as a homing device to guide other immune cells in the body to follow and attack the tumor cells.3

Dr. Vieweg is encouraged by the results: “We see a lot of patients with stable disease,” he says. “The tumors don’t shrink, but they don’t grow as expected, either.4 Some of these patients are alive for more than 12 months after receiving the vaccine in our clinical trials.”5

Dr. Vieweg says that cancer can create a biochemical environment that can outsmart the human system by increasing cells in the bloodstream that counteract vaccines, limiting their effects. He advocates a “one-two punch,” by giving what he calls a “small tickle of chemotherapy” to patients before the vaccine.

“The notion of enhancing survival with minimal toxicity is very appealing to patients. This is especially true now, more than ever before, since the FDA approved Provenge,” says Dr. Vieweg.6

Nora Disis, MD, professor of medicine at the University of Washington, and her research team, who are working toward a breast cancer vaccine, are excited by the hundreds of vaccines in the pipeline. Dr. Disis says that many of these vaccines represent novel strategies designed to highly stimulate immune response.

Dr. Disis has developed a vaccine for breast cancer, for example, that targets HER2/neu—a particular protein involved in normal cell growth that is amplified in 20 to 30 percent of breast cancers. The vaccine has shown promising results in women who have been treated for advanced cancer and are now disease-free but at high risk of relapse.

“One study we published recently in the Journal of Clinical Oncology was a Phase I/II study with 22 patients. We show that at median follow-up time of 36 months, about 85 percent of these women with metastatic breast cancer are still alive. And recently, we did a 52-month follow-up and about 75 percent are still alive. This vaccine appears very promising in providing clinical benefits in this very advanced population.” Dr. Disis’s research has also found that women do especially well when this vaccine is combined with Herceptin® (trastuzumab).7

Dr. Disis and her team are now developing an inexpensive, multiantigen vaccine and are aiming to start human clinical trials in 2012. This vaccine targets not just the HER2/neu protein but also other immunogenic proteins in breast cancer.

“What we are trying to do is design this vaccine so when your normal breast cells begin to become cancerous, your immune system can step in and start eliminating those cells.”

Over the long term, if she can get enough evidence to ensure the safety of this vaccine, Dr. Disis hopes to offer it to women with a high risk of developing breast cancer who have never had the disease. “That is our 10-year plan.”

Into the Marketplace

“I am a cancer investigator at a university,” says Dr. Vieweg. “It is my mission to find better treatment modalities for our patients. Yet we also have to find ways to get industry support in moving these drugs along through clinical trials and into the market. Ultimately, we all have to work together, including getting the FDA’s approval, to find ways to improve the mortality of cancer patients. It is up to us all.”

Dr. Disis agrees: “Pharmaceutical companies must become interested in preventive cancer vaccines. At the end of the day, who else is going to manufacture and sell these vaccines that have been shown to work?

“I’d love to let women with breast cancer, whom we love so much, know that you have a huge team of people behind you who are trying to solve this problem. It is our life’s work. And I think with all the new therapies coming out right now—really based on the investment our country has made in science over the past 15 years—there are lots of therapies for breast cancer that will keep you going until we find the cure. So hang in there with us until we do.” 

A World Without Vaccines

In 1998, Charles Shubin, MD, associate professor of pediatrics at the University of Maryland and assistant professor of pediatrics at Johns Hopkins University, was working in Uganda as a visiting professor. Upon his first visit to a local hospital’s pediatric ward, he was stunned by what he saw: Lying in the beds were perhaps 50 kids with raging measles infections. More young patients filled three additional wards, sick with not only measles but tetanus and polio—diseases we don’t see in the United States.

“Each day there were dozens of kids dying from measles,” he says. “I remember measles when I had it as a kid because there was no vaccine back then. But I had not seen much measles in my 40 years as a pediatrician.”

We are not as aware as we need to be of how far we have come—and why—says Dr. Shubin. We don’t see these diseases in this country anymore because we immunize kids. Elsewhere, however, measles alone takes the lives of 18 girls and boys each hour.8

Vaccines have clearly changed the health landscape of America, but we can easily lose what we have, Dr. Shubin cautions. He points to controversial research published in theLancet in 1998 that questioned the safety of the measles/mumps/rubella (MMR) vaccine, suggesting a possible link to autism.9

“There is no link, and there never was one. But afterward Great Britain no longer required MMR vaccines for kids entering school. A couple of years later, kids were dying of measles.”

The Lancet retracted the article earlier this year.10 In many ways, though, the damage had already been done. Says Dr. Shubin, “Moms ask me, ‘Would you give this vaccine to your own child?’” His answer is unequivocal: “‘Absolutely,’ I tell them. ‘The benefit to vaccines is so huge that you have to be willing to accept some risk. Life is not 100 percent.’” Ultimately, he says, “I treat my patients the way I treat my own kids. And I can sleep at night.”

References

1. Cancer Vaccines. ClinicalTrials.gov Web site. Available at: http://clinicaltrials.gov/ct2/results?term=CANCER+VACCINES. Accessed June 28, 2010.

2. Cancer Vaccines Fact Sheet. National Cancer Institute Web site. Available at: http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines. Accessed June 28, 2010.

3. Ask the Expert: Duke doctors excited about therapeutic cancer vaccine. American Federation for Aging Research Web site. Available at: http://websites.afar.org/site/PageServer?pagename=IA_expert_vieweg. Accessed June 28, 2010.

4. Su Z, Dannull J, Yang BK, et al. Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. Journal of Immunology. 2005;174(6):3798-807.

5. Su Z, Dannull J, Heiser A, et al. Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Research. 2003;63(9):2127-33.

6. Winslow R. Novel Cancer Treatment Cleared. Wall Street Journal. April 30, 2010.

7. Disis ML, Wallace DR, Gooley TA, et al. Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. Journal of Clinical Oncology. 2009;27(28):4685-92.

8. Measles: Key Facts. World Health Organization Web site. http://www.who.int/mediacentre/factsheets/fs286/en/index.html. Accessed June 28, 2010.

9. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive development disorder in children. Lancet. 1998;351:637-41.

10. Retraction—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 2010;375(9103):445.