Vaccine Information
Cancer Vaccines Information
Cancer vaccines are one type of cancer immunotherapy, which uses the body’s immune system against the disease. Cancer vaccines come in two flavors: therapeutic, which are aimed at treating an existing cancer, and prophylactic, which are designed to prevent disease. The vast majority of cancer vaccines are in the former category, with several in large clinical trials. One prophylactic vaccine for hepatitis B virus, which is associated with liver cancer – has Food and Drug Administration approval. A second non-therapeutic vaccine has been approved for HPV by Merck. There is a possibilitly another cervical cancer vaccine will be FDA approved by GSK.
Treatment vaccines attempt to strengthen the body’s natural immune defenses against cancers already present. The immune system needs this help; it generally doesn’t consider cancer cells as foreign – and harmful. “Antigens” on the surface of cancer cells that are supposed to get the immune system’s attention often don’t – at least not enough, and are still considered “self.”
Cancer vaccines are aimed at preventing the growth of existing cancer or halting the return of already treated cancers. They are designed to be specific, affecting only cancer cells, taking advantage of their unique characteristics. They usually have few side effects.
There are several types of treatment vaccines under study, and these are based on a number of different strategies. Every type, however, works under the premise of using the body’s immune system to fight the cancer, which might entail making the cancer appear foreign – and more visible – to the immune system while at the same time, boosting the system’s response.
There are several ways to attempt to do this. Some techniques entail altering the amino acid sequence of an antigen, for example, while others might involve putting a gene for an antigen or an immune system-boosting molecule into a viral vector to deliver to the tumor.
Cancer vaccines can also be for specific cancers, such as melanoma or prostate, and they can be more generic, “one size fits all.” Tumor cell vaccines are the most common, and use cancer cells either from the patient (autologous) or from one or more other patients’ cells grown in the laboratory (allogeneic). Tumor cell vaccines use killed cells removed during surgery. Cells are injected into the patient to rouse an immune response. Usually, the cell has been modified by a chemical or a gene to make it more effective in boosting the immune system.
Whole tumor cells, rather than specific antigens, may be used because they contain a number of antigens, some of which have not been identified, and might be more effective as a vaccine.
Autologous vaccines, while promising, have some drawbacks. Though they have the advantage of being specific for each patient’s disease, they are expensive and labor intensive to create. The idea behind allogeneic vaccines is that they could work for every patient with a particular kind of cancer.
Several other vaccine varieties are being studied. One type of vaccine uses dendritic cells, specialized white blood cells that “present” cancer cell antigens to the immune system’s T cells, helping them recognize the cancer. Dendritic cell vaccines consist of dendritic cells taken from the blood, “taught” to display antigens, then injected back into the body.
Antigen vaccines use whole or parts of proteins called peptides to coax the immune system to fight cancer cells. Antigens are combined with additional chemicals to increase an immune response. Several antigens can be combined in a single vaccine.
Anti-idiotype vaccines are based on the fact that antibodies themselves can act as cancer antigens, triggering an immune response. Antibodies produced by certain cancer cells – B cell lymphomas, for example – are called idiotype antibodies and are unique to each individual. Lymphomas might be the most promising targets for anti-idiotype vaccines. Lymphoma cells have unique antigens not present on healthy lymphocytes and other cells in the body. These antigens can be the basis for lymphoma vaccines.
DNA vaccines take advantage of the DNA sequence of tumor antigens to produce the antigen proteins. The idea is that by injecting DNA containing the gene for a specific antigen, certain cells will take up the gene and continuously make the antigen, to which the immune system will respond.
Latest Research Directions
More than 15 vaccines currently are in trials for a range of diseases, including lymphoma, melanoma, breast, lung, prostate and colorectal cancers, with mostly mixed results to date. Some of the more highly touted vaccines include:
- The M-Vax melanoma vaccine, 17 years in development, is an autologous vaccine developed by AVAX Technologies, Inc., of Kansas City, Mo., tailor-made from the patient’s cells. Several years ago, a phase 2 trial found that 45 percent of patients who had surgery and received the vaccine lived for at least five years, compared to only 25 percent of those in the past who had surgery alone. The vaccine became mired in manufacturing and regulatory issues, which delayed further testing.
- Canvaxin, a melanoma vaccine made by CancerVax Corp. of Carlsbad, Calif., is a one-size-fits-all consisting of cells from three melanoma cell lines and a weakened tuberculosis bacteria. Preliminary study results showed that the vaccine helped stage 3 melanoma patients live slightly longer. But the company recently halted its phase 3 randomized trial when interim results showed no evidence of survival benefit from the vaccine.
- In 2005, an uncontrolled trial of Provenge, an experimental cancer vaccine made by Seattle-based Dendreon, showed that men with advanced prostate cancer lived longer, though it did little to stop disease progression. The vaccine uses the patients' own dendritic cells engineered to express a protein found on about 95 percent of prostate cancer cells.
Another model takes advantage of the immune system’s response to genetically engineered bacteria such as listeria, which while sufficiently weakened to be unable to cause disease, can carry cancer antigens. The immune system’s first line of defense attacks the bacteria while sending chemical signals – cytokines – to call up the heavy hitting, cell-killing immune system troops. Several vaccines of this type are in various stages of development.
One promising avenue of research uses an antibody to block the activity of a protein called CTLA-4, which normally suppresses the immune response. By taking the brakes off of the immune response, scientists hope the antibody – called MDX-10 and made by Princeton, N.J.-based Medarex – will be effective in clinical trials for metastatic melanoma. Early trial results have been encouraging.
In the last several years, researchers have been exploring early trials with adding immune-boosting molecules such as GM-CSF and interleukin-2, and some are entering mid- and latter-stage testing. Scientists are also learning how to use cancer vaccines in combination with other therapies, such as radiation and chemotherapy, as well as newer targeted therapies.
Many scientists today are calling for a paradigm shift in how cancer vaccines are viewed. Some researchers are finding that vaccines seem to affect the immune system enough to keep cancers at bay, with tumors neither progressing nor regressing, with patients are living longer as a result. Many think that vaccines may not necessarily cure a cancer, but rather make it a chronic disease people can live with.
There are several theories why cancer vaccines have not been very successful to date. One reason is because the tumor antigens tested have been unable to elicit a sufficiently strong immune reaction. Another explanation is because many individuals receiving treatment with cancer vaccines have already had – and failed – conventional chemotherapy and radiation, weakening their immune system and their responses to vaccines. The cancer is usually too much for even a boosted – but exhausted – immune system to eliminate. Cancer cells also can “learn” to evade the immune system. Mounting evidence from both animal and human studies showing that patients with minimal disease have better outcomes with cancer vaccines than those who are sicker – and who tend to be the patients who receive vaccines.
Discovery and Early Research
The notion of a cancer vaccine has been around for more than a century. In 1893, William B. Coley of Memorial Hospital in New York developed a primitive “vaccine.” The scientific basis for immunotherapy for cancer dates back some 50 years. In the 1950s, Richmond Prehn, while at the National Cancer Institute, demonstrated that mice could be immunized against chemically induced tumors.
In the early 1970s, pioneers such as a David Berd and Michael Mastrangelo at Jefferson Medical College in Philadelphia, Malcolm Mitchell, now at the University of California at San Diego, Donald Morton, at the John Wayne Cancer Institute in Santa Monica, Calif., Lloyd Old and Herbert Oettgen at Memorial Sloan-Kettering and others began testing early generation melanoma vaccines.
Steven Rosenberg at the National Cancer Institute showed in the 1980s that IL-2 could be used to treat tumors in patients with melanoma and renal cancer. In addition, Ronald Levy at Stanford, using monoclonal antibodies against idiotype antigens displayed by lymphoma, and Alan Houghton at Memorial Sloan-Kettering, using monoclonal antibodies against a self-antigen on melanoma, found that targeting tumors with antibodies was an effective therapy. A major step occurred in 1991 when researchers discovered the first human cancer cell antigen recognized by T cells.
Today, researchers are capitalizing on new-found knowledge gained over the last decade of how the immune system works. At the same time, an enormous amount of research in recent years has focused on discovering new tumor antigens and new viral vectors that can deliver genes for such antigens. The latter entails inserting a gene for a tumor antigen into a virus or bacteria, along with genes for substances that jump start the immune system.
The molecular identification of such “adjuvants” – cytokines, GM-CSF and T-cell co-stimulatory molecules, for example – which make cancer more visible to the immune system, is one of the most promising innovations in recent years, and has helped make possible the development of “next generation” vaccines.
Resources
National Cancer Institute
1-800-4-CANCER
http://www.cancer.gov
American Cancer Society
1-800-ACS-2345
www.cancer.org
