“Personalized melanoma vaccines can be used to marshal a powerful immune response against unique mutations in patients’ tumors, according to early data in a first-in-people clinical trial at Washington University School of Medicine in St. Louis.
“The tailor-made vaccines, given to three patients with advanced melanoma, appeared to increase the number and diversity of cancer-fighting T cells responding to the tumors. The finding is a boost to cancer immunotherapy, a treatment strategy that unleashes the immune system to seek out and destroy cancer.
“The research is reported April 2 in Science Express, in a special issue devoted to cancer immunology and immunotherapy.”
“An experimental therapeutic vaccine from Danish drugmaker Bavarian Nordic helped significantly extend survival in patients with advanced prostate cancer, according to results of a small early-stage trial conducted by the U.S. National Cancer Institute.
“Shares of Bavarian Nordic closed up almost 12 percent in Copenhagen after the company released the data on Tuesday.
“The study involved 30 patients with prostate cancer that had failed to benefit from standard treatments that reduce levels of testosterone, the male hormone that fuels the cancer.
“Patients were treated with the company’s Prostvac vaccine, in addition to escalating doses of Bristol-Myers Squibb Co’s Yervoy, an approved injectable treatment for advanced melanoma that works by taking the brakes off the body’s immune system.”
Editor’s note: The immune system-boosting treatment discussed in this article has not yet been tested in patients. Nonetheless, this article provides a good explanation of cancer vaccines.
“NIBIB-funded researchers have developed a novel 3D vaccine that could provide a more effective way to harness the immune system to fight cancer as well as infectious diseases. The vaccine spontaneously assembles into a scaffold once injected under the skin and is capable of recruiting, housing, and manipulating immune cells to generate a powerful immune response. The vaccine was recently found to be effective in delaying tumor growth in mice.
” ‘This vaccine is a wonderful example of applying biomaterials to new questions and issues in medicine,’ says David Mooney, Ph.D., a professor of bioengineering at Harvard University in the School of Engineering and Applied Sciences, whose lab developed the vaccine. The project was co-led by Jaeyun Kim, Ph.D. and Aileen Li, a doctoral student in the Mooney lab. Their findings were published in the December 8, 2014 issue of Nature Biotechnology.
“Cancer cells are generally ignored by the immune system. This is because — for the most part — they more closely resemble cells that belong in the body than pathogens, such as bacterial cells or viruses. The goal of cancer vaccines is to provoke the immune system to recognize cancer cells as foreign and attack them.
“One way to do this is by manipulating dendritic cells, the coordinators of immune system behavior. Dendritic cells constantly patrol the body, sampling bits of protein found on the surface of cells or viruses called antigens. When a dendritic cell comes in contact with an antigen that it deems foreign, it carries it to the lymph nodes, where it instructs the rest of the immune system to attack anything in the body displaying that antigen.”
The gist: A new cancer vaccine has shown promise for patients in a clinical trial in Singapore. The vaccine, called TAA/ecdCD40L, is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. So far, only four patients have received the vaccine, including two with breast cancer and two with ovarian cancer. They have had no significant side effects. Time will tell if the vaccine works well against cancer.
“The National Cancer Centre Singapore (NCCS) has launched a clinical trial of a new cancer vaccine administered to human patients for the first time in the world. Cancer immunotherapy (the harnessing of the body’s defence system to fight the patient’s cancer, has emerged as one of the most exciting medical breakthroughs in the past two years.
“In fact, the prestigious Science journal voted Cancer Immunotherapy the Breakthrough of the Year for 2013. Cancer Immunotherapy includes cancer vaccines, a form of treatment aimed at stimulating the body’s immune cells to attack a target protein on cancer cells. This particular cancer vaccine encodes one of the most common proteins, MUC-1 that is expressed on many cancers, including ovarian, breast, prostate, colon, pancreas and lung cancer, but not expressed on normal cells.
“The Singapore Clinical Research Institute (SCRI), a wholly-owned subsidiary of MOH Holdings, sponsored this clinical trial providing support that included project oversight, study drug importation, quality assurance and providing the medical expertise required in conducting a cancer trial.”
The gist: A new vaccine treatment called Prostvac might help treat advanced prostate cancer patients whose tumors are resistant to hormone therapy and who have had either surgery or radiation. Prostvac boosts a patient’s own immune system to fight cancer. A small clinical trial showed that Prostvac is safe and can be given to patients earlier. More research is needed to see just how well the vaccine works.
“Aiming to increase treatment options for prostate cancer patients who have an early relapse, investigators from a multi-institutional cooperative group — including Rutgers Cancer Institute of New Jersey — have demonstrated that a vaccine therapy that stimulates the body’s own immune defenses can be given safely and earlier in the course of prostate cancer progression.
“As part of a Phase II clinical trial, adult patients with advanced prostate cancer (as evidenced by two rising prostate-specific antigen or PSA values and no visible metastasis) whose cancer is resistant to hormone therapy and had either surgery or radiation were recruited from member institutions in the ECOG-ACRIN Cancer Research Group. In their work, published in the current online edition of European Urology, ECOG-ACRIN investigators examined two different experimental treatment options.
“In step one, patients were treated with PROSTVAC-V/TRICOM and PROSTVAC-F/TRICOM. PROSTVAC-V is derived from a vaccinia virus that was used for many years to vaccinate against smallpox. This virus is modified to produce a PSA protein that helps focus the body’s immune response to the PSA in the prostate tumor. In addition, it is modified to produce three other proteins that help increase an immune cell’s ability to destroy its target (TRICOM). PROSTVAC-F is made from the fowlpox virus, which is found in birds and not known to cause any human disease. It contains the same genetic material as PROSTAC-V, but is given multiple times to further boost the body’s immune system.”
The gist: A treatment that boosts the immune system to fight cancer has shown promise for breast cancer patients. The treatment is a cancer vaccine known as the MAM-A DNA vaccine. It was tested in volunteer patients in a clinical trial. It is meant to treat people whose tumors have a protein called mammaglobin-A. The trial showed that the MAM-A DNA vaccine is safe, and may even slow cancer progression. Further studies will show just how effective it might be.
“An initial safety trial of a breast cancer vaccine has proven safe, with preliminary results suggesting the vaccine will slow cancer progression.
“The vaccine, which is being developed by researchers at Washington University School of Medicine in St. Louis, is meant for patients with breast cancers that express a protein found only in breast tissue called mammaglobin-A.
“Tumors express a very high level of the protein, and research shows it’s present in up to 80% of breast cancers. That means if the vaccine makes it to market, it could potentially be beneficial to a very high number of breast cancer patients.
“The vaccine works by making the immune system focus and destroy cells with the mammaglobin-A protein. In a recent trial to test the vaccine’s safety published in the journal, Clinical Cancer Research, the researchers tested the vaccine in 14 breast cancer patients with mammaglobin-A.
Among solid tumors, the curative potential of immunotherapies has been explored most in melanoma. One reason for this is that melanoma tumors often contain so-called immune infiltrates—patches of T cells, the killer cells of the immune system. It seems that these fighter cells arrive at the ‘battlefield’ to target tumor cells for killing, but instead become ‘frozen,’ unable to attack. How to activate the tumor-killing potential of T cells has been an area of intense and fruitful research, leading to the development of several immunotherapy drugs. Continue reading…
The gist: Cancer vaccines are a form of immunotherapy—treatment meant to boost a patient’s own immune system to fight cancer. Unfortunately, they have not proven very successful when tested in lung cancer patients in clinical trials. The disappointing trend continues with new results from a clinical trial testing a vaccine called MAGE-A3. However, we posted a story yesterday about scientists’ hopes that cancer vaccines may start working better when paired with certain drugs called checkpoint inhibitors.
“The MAGRIT trial showed disappointing results for a developmental vaccine called MAGE-3 in patients with non–small cell lung cancer (NSCLC) who had undergone surgical resection. This is the largest vaccine trial conducted in lung cancer, and investigators hoped that an immunotherapy approach with a vaccine would improve outcomes. The findings were presented at the ESMO 2014 Congress in Madrid (Abstract 1173O).
“At present, about 45% of patients are cured by surgery with or without chemotherapy, and better therapies are needed.
“ ‘Vaccinations give us effective soldiers, but in this case they didn’t work on the battlefield,’ stated lead author Johan F. Vansteenkiste, MD, Catholic University Leuven, Belgium. He noted that other trials have shown that lung cancer vaccines elicit antibodies and immune cells (ie, “soldiers”) that can kill cancer cells, ‘but the problem occurs when they come to the battlefield, ie, the environment of the tumor where they are paralyzed by factors in the tumor.’
“On the plus side, the MAGE-3 cancer vaccine was well tolerated and the investigational effort identified a predictive marker for treatment benefit—the MAGE-A3 protein. Of the nearly 13,500 NSCLC patients screened for the study, one-third had tumors that expressed MAGE-A3—similar to the expected distribution in NSCLC.”
“Using vaccines to fight cancer is a field littered with failures but experts believe it is possible the approach could get a new lease of life if such shots are combined with a new class of drugs called checkpoint inhibitors.
“Unlike traditional preventative vaccines, therapeutic cancer vaccines are designed for people with established disease and are supposed to boost the patient’s immune system to keep tumors at bay.
“Unfortunately, the theory has not worked out in practice because, while the vaccines are successful at triggering a response from the ‘foot soldiers’ of the immune system, cancer cells still manage to escape detection.
“The result has been a series of failures with high-profile experimental cancer vaccines such as Merck KGaA’s Stimuvax and GlaxoSmithKline’s MAGE-A3.
“GSK threw in the towel on its vaccine in April, dashing hopes for a project that was once seen as a potential multibillion-dollar sales opportunity in lung cancer and melanoma.”