Cancer Vaccines: Part II

Nearly 1.5 million people in the United States were estimated to have been diagnosed with cancer in 2009, according to the American Cancer Society. Although an amazing variety of drugs has been developed to fight cancer, it remains the second leading cause of death in this country (the first is heart disease), claiming the lives of just over half a million Americans last year. It is responsible for nearly one in four deaths in America.

Clearly, better approaches are needed to effectively fight cancer. An emerging alternative to traditional drugs is cancer vaccines, which function by stimulating the patient’s own immune system to fight the cancer. The first therapeutic cancer vaccine to be approved by the FDA, a vaccine called Provenge which is used to treat prostate cancer, just received its approval this Thursday, April 29, 2010, and many other cancer vaccines also have promising results from clinical trials.

Just like flu vaccines, cancer vaccines are intended to stimulate an immune response from the patient to reject a “foreign” material. There are two main groups of cancer vaccines based on what they target: “preventative” and “therapeutic.” Preventative cancer vaccines immunize against viruses that cause cancers, such as hepatitis B and the human papillomavirus (the viruses that cause cervical and liver cancer, respectively). There are successful, FDA-approved preventative cancer vaccines for these viruses, which were discussed last week in “Biology Bytes: Cancer Vaccines, Part I.” This week, the second group of cancer vaccines will be explored: therapeutic cancer vaccines.

Therapeutic cancer vaccines are designed to help patients who already have cancer. The goal is to make the body have an immune response against the cancer, so that the body can effectively fight it. Because cancer is made up of cells from the patient, it is not truly a “foreign” material and so it is normally difficult for the immune system to identify it as a threat. Consequently, cancer can hide from the immune system, avoiding detection and attack.

The key principle of cancer vaccines is that the immune system needs help, or stimulation, to recognize the cancer as a threat and attack it. Cancer vaccines usually contain some component of the cancer, either parts of proteins and cells or entire cells, to give the immune system a clear target to attack. However, researchers have to be particularly careful about what they make a cancer vaccine out of: If a protein is made by many cells other than the tumor cells, the normal cells may be accidentally targeted.

This has been greatly overcome by identifying proteins that only tumors make in large amounts. Although it is much harder to develop therapeutic cancer vaccines than preventative ones because of these complications, therapeutic cancer vaccines are being tested in clinical trials for lung, colorectal, breast, prostate, melanoma, lymphoma, and kidney cancers, and many have yielded promising results and may be nearing FDA-approval. So, what cancers are these vaccines targeting?

Lung Cancer: The most common malignant cancer is lung cancer, killing more people each year than any other cancer: the National Cancer Institute of the U.S. National Institutes of Health estimated that in 2009 lung cancer killed nearly 160,000 people in the United States (while 220,000 new cases were diagnosed). A therapeutic cancer vaccine for non-small cell lung cancer (NSCLC) (which makes up the majority of lung cancer cases) is in phase III clinical trials. The vaccine, called Lucanix (Belagenpumatucel-L), is produced by a San Diego-based biopharmaceutical company, NovaRx Corporation.

Lucanix is intended to fight NSCLC by interfering with a protein called transforming growth factor-beta (TGF-beta). TGF-beta is often elevated in patients with NSCLC, which causes the immune system to become suppressed and not attack the cancer. Lucanix is made up of four types of (dead) lung cancer cells that have been genetically modified to inhibit the secretion of TGF-beta, ideally increasing the ability of the patient’s body to identify the cancer as an “invader” and fight it off. In phase II clinical trials, patients with advanced NSCLC lived an average of 16 months longer with Lucanix. The NovaRx Corporation has become the first to demonstrate that inhibiting TGF-beta can increase the body’s immune response to a tumor, which may result in longer survival. This approach could potentially be applied to other cancers. Although no unusual negative side effects have been reported, caution must be used; TGF-beta has other key roles in the body (such as preventing cells from growing out of control), and care must be taken to ensure that other functions are not undesirably disrupted.

Lucanix is just starting phase III clinical trials for treating non-small cell lung cancer. The Cancer Center of Santa Barbara, under Dr. Fred Kass, is one of nearly 60 centers around the world involved in the phase III clinical trials (as was previously covered at The Santa Barbara Independent by Ethan Stewart). While Lucanix is not a cancer cure, it may be a relatively significant step in the right direction for improving the lives of patients with lung cancer. If successful, these clinical trials may be the last step before FDA-approval.

Colorectal Cancer: Colorectal cancer is the second leading cause of cancer death in the United States, causing nearly 50,000 deaths in 2009, while around 147,000 people in the country were newly diagnosed. An appealing target for these cancer treatments is a protein called 5T4. 5T4 is made in high amounts by many different types of cancers (colorectal, ovarian, gastric, and kidney) but only rarely in other cells, and is believed to be involved in cancer metastasis. Oxford BioMedica, a United Kingdom-based biopharmaceutical company, developed a cancer vaccine to target 5T4 called TroVax. TroVax delivers the blueprints for 5T4 in a modified (benign) virus, just like a typical vaccine, the aim being to stimulate an immune response against the 5T4 protein.

In phase II clinical trials, TroVax was tested in more than 200 patients and 95 percent showed “potent and sustained immune responses” with minimal side effects. Phase III clinical trials started in 2008, but underwent a series of amendments recommended by the FDA. The FDA is currently reviewing the data collected so far to recommend possible guidance for approval. Clinical trials have been testing the efficacy of TroVax to treat kidney and prostate cancers as well.

Breast Cancer: An estimated 40,000 women died from breast cancer in 2009. Mucin 1, or MUC1, is a protein made in high amounts by many different types of cancers: aside from breast cancer, it is also in prostate, lung, and colorectal cancers. Merck and Oncothyreon (a German pharmaceutical company and a Seattle-based biotechnology company, respectively) have created a cancer vaccine called Stimuvax to target MUC1. Stimuvax contains a short, synthetic protein that ideally generates an immune system response specifically against MUC1, consequently destroying the cancer cells that make it. After promising results in early clinical trials, in 2009 phase III clinical trials on Stimuvax started for breast cancer as well as lung cancer. However, just last month it was announced that further recruitment of participants was halted after one patient from a phase II trial contracted encephalitis (a serious condition caused by inflammation of the brain).

Additional breast cancer vaccines are being developed against other probable targets, such as human epidermal growth factor receptor 2, or HER-2. This growth factor, produced in abnormally high levels in 20-25 percent of breast cancers, is already a target of breast cancer drugs Trastuzumab and Lapatinib.

Prostate Cancer: Prostate cancer claimed the lives of around 27,000 Americans last year. The Dendreon Corporation, a Seattle-based biotechnology company, produced a prostate cancer vaccine called Provenge (sipuleucel-T), which, as of Thursday, April 29, 2010, just became the first FDA-approved therapeutic cancer vaccine. Provenge aims to trigger an immune response against the cancer cells by zeroing-in on a protein made in large quantities by prostate cancers, called prostatic-acid phosphatase (PAP). The vaccine contains a patient’s own blood cells that have been modified to make PAP. Clinical trials showed an average four months’ increase in survival time, significantly better than current alternative prostate cancer drugs. As the first FDA-approved therapeutic cancer vaccine, Provenge holds much promise for treating patients with prostate cancer.

Other cancers, such as non-Hodgkin lymphoma, kidney cancer, and melanoma, also have various vaccines that are in clinical trials. A phase III clinical trial for treating follicular lymphoma (a type of non-Hodgkin lymphoma) with the cancer vaccine BiovaxID showed remission time to be increased by just over a year. A cancer vaccine called Oncophage, made by the New York-based company Antigenics, has been approved in Russia for treating kidney cancer. Trials showed it to increase survival by a year in some patients, although for FDA approval in the U.S. new trials are required. Cancer vaccines for melanoma are also being explored; BioVex Inc. created the vaccine OncoVEX GM-CSF, which contains a virus that only replicates in the melanoma tumor and creates proteins to stimulate the immune response there, enhancing rejection of the tumor. OncoVEX GM-CSF is currently in phase III clinical trials for melanoma.

With so many different therapeutic cancer vaccines in clinical trials and many showing very encouraging results, the outlook is bright for these novel cancer treatments. Others may soon be following the way of Provenge in receiving FDA-approval and become important weapons in doctors’ ever-expanding arsenal to better fight cancer.

Next week: The concluding article of the cancer vaccine series will discuss using embryonic tissues and cells to vaccinate against cancer.

For more on cancer vaccines, see the U.S. National Institutes of Health: National Cancer Institute’s amazing fact sheet on cancer vaccines, including a list of active clinical trials of cancer vaccines, their list of common cancers in the United States, or a review of “Cancer Vaccines: a new frontier in prevention and treatment.”

Biology Bytes author Teisha Rowland is a science writer, blogger at All Things Stem Cell, and graduate student in molecular, cellular, and developmental biology at UCSB, where she studies stem cells. Send any ideas for future columns to her at science@independent.com.