The Unfolding Landscape of Cancer Vaccine Development
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Our immune cells can detect and destroy cancerous cells by recognizing molecular features on their surface. However, the function of these immune cells can be suppressed, or they can be manipulated into encouraging tumor growth, invasion and metastasis.
Cancer vaccines are a type of immunotherapy that may be preventative, therapeutic or personalized. Preventative vaccines seek to protect the body by alerting the immune system to the presence of an oncovirus, so it can be cleared before it causes a cancer-associated infection. In contrast, therapeutic vaccines aim to strengthen existing immune responses against cancer and personalized vaccines target unique features on cancer cells that arise from specific mutations. Here, we take a look at the latest advances in cancer vaccine development and testing.
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In a Phase III clinical trial, a vaccine was found to extend survival by many months or – in some cases, years – in patients with glioblastoma, the most aggressive form of brain tumor in adults.
The trial was conducted over 8 years and involved more than 300 glioblastoma patients from the UK, USA, Canada and Germany. The vaccine was produced for each individual patient by isolating specific immune cells known as dendritic cells. The isolated dendritic cells were then primed with biomarkers from a sample of the patient’s tumor, and injected back into the patient. This allowed the immune system of each patient to recognize and mount a personalized attack on the target cancer cells.
All participants underwent the standard treatment for glioblastoma of surgery followed by radiotherapy and chemotherapy. Two thirds of the cohort then received the vaccine, and the final third were assigned as a control group, receiving a placebo. Patients with a new glioblastoma diagnosis treated with the vaccine survived 19.3 months on average, compared to 16.5 months for the control group. Approximately 13% of patients treated with the vaccine survived at least 5 years from diagnosis, compared to 5.7% in the control group.
“The vaccine was shown to prolong life, and interestingly so in patients traditionally considered to have poorer prognosis. For example, we see clear benefits in the older patient groups as well as in those patients in whom radical surgery was not possible for technical or other reasons.” – Dr. Keyoumars Ashkan, professor of neurosurgery at King’s College Hospital, and European chief investigator of the clinical trial.
In a study published in JAMA Oncology, a newly developed experimental vaccine was shown to safely generate an immune response against an important driver of breast cancer growth, human epidermal growth factor receptor (HER2).
HER2 is found on the surface of cells and regulates their growth and division. In around 30% of breast cancers, HER2 is overproduced, and these “HER2-positive” cancer cells can go on to produce hundreds of times the normal amount of HER2, leading to uncontrolled cell proliferation.
Patients that produce a strong cytotoxic immune response against their HER2-positive cancers typically have longer overall survival and a lower chance of recurrence than those who don’t. Senior study author Dr. Mary “Nora” L. Disis, professor of medicine at the University of Washington and director of the Cancer Vaccine Institute, and colleagues set out to target and stimulate this anti-HER2 immune response by developing a DNA vaccine. The vaccine, designed with the instructions for part of the HER2 protein that is found within the cell, successfully generated the desired cytotoxic immune response without severe side effects.
“The results showed that the vaccine was very safe,” Disis said. “In fact, the most common side effects that we saw in about half the patients were very similar to what you see with COVID vaccines: redness and swelling at the injection site and maybe some fever, chills and flu-like symptoms.”
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Senescence is a state of latency reached by damaged or aged cells in which they do not reproduce, but do not disappear. Senescent cells emit information signals that warn of their presence, stimulating an inflammatory response and tissue regeneration. Research published in Cancer Discovery has shown that, after vaccinating healthy mice with senescent cancer cells and then stimulating the formation of tumors, the animals did not develop cancer, or only a significantly reduced number did.
According to this research, senescent cells, due to their characteristics, are a good option for activating the immune system and improving its response to the tumor. As they are alive, senescent cells remain in the body longer than dead ones and can stimulate the immune system for longer. On the other hand, as these cells do not divide, they cannot regenerate the tumor.
"Our results indicate that senescent cells are a preferred option when it comes to stimulating the immune system against cancer, and they pave the way to considering vaccination with these cells as a possible therapy," – Dr. Manuel Serrano, head of the Cellular Plasticity and Disease lab at IRB Barcelona.
Results from mouse models and human cells show that a modified tuberculosis vaccine could help treat non-muscle invasive bladder cancer without strong side effects.
The study, published in Cancer Immunology, Immunotherapy, used a modified version of the Bacillus Calmette–Guérin (BCG) vaccine, developed for tuberculosis in the 1920s. Since the 1970s, The BCG vaccine has been used to treat non-muscle invasive bladder cancer by stimulating an immune response at the cancer site. It is more effective than chemotherapy for this type of cancer, but up to 84% of patients cannot tolerate its strong side effects, and do not complete the treatment. When treatments fail, the last option is to remove the bladder, which leads to reduced quality of life.
By removing certain lipids from the cell envelopes of the bacteria in the BCG vaccine, the researchers were able to produce a “delipidated” vaccine, which still triggers the body to produce well-regulated immune responses but reduces the inflammation that causes severe tissue damage.
“It is more targeted and allows for a longer, slower response, which makes it more effective,” – Dr. Jordi Torrelles, professor at Texas Biomedical Research Institute.