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Cancer Vaccine Shows Promise For Patients With Stage III And IV Kidney Cancer
Dana-Farber Cancer Institute researchers report that all nine patients in a clinical trial being treated for stage III or IV clear cell renal cell carcinoma (a form of kidney cancer), generated a successful anti-cancer immune response after initiation of a personalized cancer vaccine. The vaccines were administered after surgery to remove the tumor and are designed to train the body's immune system to recognize and eliminate any remaining tumor cells. At the time of data cut-off (median of 34.7 months), all patients remained cancer-free.
The results of this phase 1 trial were reported today in Nature.
"We're very excited about these results, which show such a positive response in all nine patients with kidney cancer," says co-senior author and co-principal investigator Toni Choueiri, MD, Director of the Lank Center for Genitourinary Cancer at Dana-Farber.
"This study was the result of a close partnership between our NeoVax team, our colleagues at the Broad Institute of MIT and Harvard, and our colleagues at the Lank Center for Genitourinary Cancer at Dana-Farber," says co-senior author Catherine Wu, MD, chief of the Division of Stem Cell Transplantation and Cellular Therapies at Dana-Farber and an institute member at Broad, who developed the NeoVax vaccine technology used to create the personalized cancer vaccines for this trial. "We are thrilled to report these results."
Patrick Ott, MD, PhD, director of the Center for Cancer Vaccines at Dana-Farber, and Derin Keskin, PhD, immunologist at the Center for Cancer Vaccines at Dana-Farber, are also co-senior authors. David A. Braun, MD, PhD, formerly of Dana-Farber and Harvard Medical School, and now a medical oncologist and physician-scientist at Yale Cancer Center and Yale School of Medicine is first author.
Standard treatment for patients with stage III or IV clear cell renal cell carcinoma is surgery to remove the tumor. Surgery can be followed by immunotherapy with pembrolizumab, an immune checkpoint inhibitor. Pembrolizumab induces an immune response that reduces the risk of the cancer coming back. However, about two-thirds of patients can still recur and have limited treatment options.
"Patients with stage III or IV kidney cancer are at high risk of recurrence," says Choueiri. "The tools we have to lower that risk are not perfect and we are relentlessly looking for more."
In this investigator-initiated trial, Choueiri and Braun treated nine patients with stage III or IV clear cell renal cell carcinoma with a personalized cancer vaccine after surgery. Five patients also received ipilimumab with the vaccine.
The vaccines are personalized to recognize the patient's individual cancer using the tumor tissue removed during surgery as a guide. The team extracts molecular features from the tumor cells that differentiate them from normal cells. These features, called neoantigens, are tiny fragments of mutant proteins that exist in the cancer but not in any other cells in the body.
The team uses predictive algorithms to determine which of these neoantigens to include in the vaccine based on their likelihood to induce an immune response. The vaccine is then manufactured and administered to the patient in a series of initial doses followed by two boosters.
"This approach is truly distinct from vaccine attempts in kidney cancer" says Braun. "We pick targets that are unique to the cancer and different from any normal part of the body, so the immune system can be effectively "steered" towards the cancer in a very specific way. We learned which specific targets in the cancer are most susceptible to immune attack and demonstrated that this approach can generate long-lasting immune responses, directing the immune system to recognize cancer. We believe this work can form a foundation for the development of neoantigen vaccines in kidney cancer."
While some patients experienced local reactions at the vaccine injection site, and some experienced flu-like symptoms, no higher-grade side effects were reported.
"The neoantigens targeted by this vaccine help steer immune responses towards cancer cells, with the goal to improve on-target efficacy and reduce off-target immune toxicity," says Choueiri.
When the team initiated this study eight years ago, it wasn't clear whether this approach could work in kidney cancer. It had been shown to have the potential to be effective in melanoma, which has many more mutations and therefore many possible neoantigens.
But kidney cancer is a disease with fewer mutations, and therefore fewer targets to manufacture the vaccine. It was important for the investigators to learn as much as possible from this early phase study about how the vaccine influences an immune response to the tumor.
Through a series of analyses, the team found that the vaccine induced an immune response within three weeks, the number of vaccine-induced T cells increased by a mean of 166-fold, and these T cells remained in the body at high levels for up to three years. In vitro studies also showed that the vaccine-induced T cells were active against the patient's own tumor cells.
"We observed a rapid, substantial, and durable expansion of new T cell clones related to the vaccine," says Ott. "These results support the feasibility of creating a highly immunogenic personalized neoantigen vaccine in a lower mutation burden tumor and are encouraging, though larger scale studies will be required to fully understand the clinical efficacy of this approach."
Clinical trials with larger number of patients are needed to confirm the vaccine's effectiveness and explore its full potential. An ongoing multicenter international randomized study uses a similar neoantigen-targeting personalized cancer vaccine will be administered in combination with immunotherapy pembrolizumab (NCT06307431). Choueiri serves as the co-chair of its Scientific Advisory Committee.
Dealing With Late-Stage Ovarian Cancer
When you're diagnosed with late-stage (stage IV) ovarian cancer, you probably have lots of questions. You might wonder, how long can you live with advanced ovarian cancer? And what happens if it progresses to end-stage ovarian cancer?
While everyone's cancer is different, you can educate yourself and take steps to help prepare for what may lie ahead.
Stage IV ovarian cancer is a "distant" stage. That means the cancer has spread far from your ovaries into places like your liver, lungs, or bones.
Your life expectancy with this type of cancer depends on factors individual to you. Your age, overall health, how well your cancer responds to treatment, and what treatment options are available to you all make a difference in your outcome.
Five-year relative survival rates compare the chances that someone with a certain type and stage of cancer will survive for 5 years, compared with the general population. For example, a rate of 50% means a person diagnosed with that cancer is 50% as likely to live at least 5 years as someone without that cancer.
Survival rates depend in part on what type of ovarian cancer you have. In people who are initially diagnosed with ovarian cancer at stage IV, the 5-year relative survival rates are:
Survival rates often improve over time as better treatments become available. These 5-year survival rates are based on information about people who were diagnosed between 2012 and 2018. When the next set of data becomes available, the rates may change.
You can ask your doctor to give you an estimate, based on your individual situation, of how long you can expect to live. While it's a hard conversation to have, the answer can help you put plans in place. That might mean taking a dream trip with your family, or taking care of important paperwork, such as wills or estate trusts.
Remember, this is your doctor's educated guess. You may have more, or less, time depending on how well you're doing.
Having stage IV ovarian cancer doesn't necessarily mean you should give up on treatment. Treatment can often help you feel better and possibly live longer.
Treatment for this stage of ovarian cancer may include some combination of surgery, chemotherapy, and the targeted medication bevacizumab (Avastin). You may also be a candidate for clinical trials, which let you contribute to research while trying a new treatment or combination of treatments.
While it's not common, it's possible in some cases to cure ovarian cancer even in its advanced stages. Some 20% of those with late-stage ovarian cancer survive more than 12 years after treatment. In medical terms, they're considered cured. Your doctor will help you determine whether continuing treatment makes sense for you.
Even when a cure isn't necessarily the goal, these treatments and others, such as pain medication, can be used as palliative care to relieve symptoms like pain, fatigue, and digestive issues.
Complementary and integrative care may help you manage the symptoms of your cancer as well as side effects of treatment. They can play a role in improving your overall well-being and quality of life. These may include:
Ask your doctor what complementary treatments you should consider, and which ones to avoid.
Ovarian cancer often doesn't have any symptoms in its early stages. Symptoms of late-stage ovarian cancer can include:
Depending on where your stage IV ovarian cancer has spread, you can start to feel symptoms in different organs and tissues.
If you have stage IVA, the beginnings of stage IV ovarian cancer, cancer cells have spread to the fluid around your lungs. You could cough, find it harder to breathe, or feel winded.
In stage IVB, the more advanced diagnosis, the cancer has spread to the inside of your spleen or liver and/or other organs or tissues such as your lungs or bones. You may also have cancer in lymph nodes other than those in your abdomen.
Learning that you may not be able to cure your cancer takes a toll. It's a hard thing to process and navigate.
Being diagnosed with ovarian cancer at any stage raises your risk for problems like anxiety, depression, stress, worry, and insomnia. One study found that, in the first 2 years after their diagnosis, women with ovarian cancer were three times more likely to have depression or anxiety than the general public.
You may also have trouble with your social life and with physical intimacy. In studies, people with ovarian cancer voiced all these concerns.
Your mental state is an important part of your overall health. If you're having a hard time, reach out for help. Many cancer centers have mental health care professionals, such as psychiatrists, psychologists, or social workers, to help people going through cancer.
Taking steps to take care of yourself can help relieve stress and give you a sense of control.
Social support. This is important for both your physical and mental well-being. Reach out to your family and friends. Often they want to do something to help, but don't know how. Ask if they can set up a meal train for you, for example, if you're having trouble cooking for yourself.
If your condition worsens, you and your family may need more support. Your cancer center or hospital can help you find resources in your community. Often, they're free or low-cost. A hospital social worker can help you look for grants or financial aid if you're having financial problems related to your condition. The American Cancer Society can also point you to sources of support.
Take care of your body. Eat as well as you can and, if your doctor approves, move your body in gentle ways that feel good. This not only helps you maintain physical strength but can help boost your mood as well.
Spiritual and emotional care. Do things that nourish your spirit, whether it's journaling, prayer, church services, a hobby, or time spent in nature.
Say no. Save your time and energy for things that really matter to you.
If treatment is no longer an option, consider hospice care. Whether you get this care at home or at a facility, the hospice team will provide social, emotional, and spiritual support to you and your family during the final stages of your illness.
Hospice nurses make regular visits to your home to help monitor your care and help guide your primary caregiver. They're often available by phone 24/7 to answer any questions or concerns.
Promising Cancer Vaccine Boosts Hope For Stage III And IV Kidney Cancer
All patients involved in the phase 1 trial of a personalized cancer vaccine for high-risk stage III/IV kidney cancer showed a successful anticancer immune response.
Today, Dana-Farber Cancer Institute announced that all 9 patients in a clinical trial (NCT02950766) being treated for stage III or IV clear cell renal cell carcinoma showed significant anticancer immune response after initiation of a personalized cancer vaccine.1
The findings from the phase 1 trial are published in Nature.2
The trial aimed to determine the safety and efficacy of a neoantigen-based personalized cancer vaccine.Image credit: radekcho - stock.Adobe.Com
"This study was the result of a close partnership between our NeoVax team, our colleagues at the Broad Institute of MIT and Harvard, and our colleagues at the Lank Center for Genitourinary Cancer at Dana-Farber," co–senior author Catherine Wu, MD, chief of the Division of Stem Cell Transplantation and Cellular Therapies at Dana-Farber and an institute member at Broad, who developed the NeoVax vaccine technology used to create the personalized cancer vaccines for this trial, said in a statement.1 "We are thrilled to report these results."
The trial aimed to determine the safety and efficacy of a neoantigen-based personalized cancer vaccine.2 Following surgical removal of the tumor, each patient received a vaccine tailored to their specific cancer mutations. Five of the 9 participants also received ipilimumab, an immune checkpoint inhibitor, alongside the vaccine.
To develop the vaccine, researchers extracted tumor samples and used predictive algorithms to identify neoantigens—unique cancer-specific protein fragments not present in normal cells. These neoantigens were selected based on their potential to trigger an immune response. The vaccine was then manufactured and administered in an initial series of doses, followed by 2 booster shots.
Renal cell carcinoma is a common cancer characterized by a relatively low mutational burden and defined cancer driver mutations. While immune-based therapies, including both cytokine-based and immune checkpoint inhibitors, have shown antitumor activity in renal cell carcinoma, the disease presents challenges due to its lower mutational burden compared with other cancers like melanoma or lung cancer.
Within 3 weeks of vaccination, there was a significant increase in the number of vaccine-induced T-cells, which expanded by an average of 166-fold.1 These T-cells remained at elevated levels for up to 3 years, demonstrating long-term persistence. In vitro studies further confirmed that the vaccine-induced T-cells were able to specifically target and attack the patients' tumor cells.
Importantly, no severe adverse events were reported during the trial, with patients only experiencing mild local reactions at the injection site or flu-like symptoms. These findings suggest that the personalized vaccine approach can effectively stimulate a durable immune response, offering hope for improving recurrence prevention for patients with kidney cancer.
These findings are particularly significant given the high recurrence rate of stage III and IV kidney cancer. Current standard treatments include surgery and immunotherapy with pembrolizumab, which reduces recurrence risk but is not effective for all patients. The study demonstrates that a personalized vaccine approach can generate a durable immune response in kidney cancer, a disease with fewer genetic mutations than melanoma, where similar vaccines have shown success.
While these early results are promising, larger clinical trials are needed to confirm the vaccine's long-term efficacy. An ongoing international randomized trial (NCT06307431) is now evaluating a similar personalized cancer vaccine in combination with pembrolizumab.
"This approach is truly distinct from vaccine attempts in kidney cancer," David A. Braun, MD, PhD, formerly of Dana-Farber and Harvard Medical School, and now a medical oncologist and physician-scientist at Yale Cancer Center and Yale School of Medicine, in the statement.1 "We pick targets that are unique to the cancer and different from any normal part of the body, so the immune system can be effectively 'steered' towards the cancer in a very specific way. We learned which specific targets in the cancer are most susceptible to immune attack and demonstrated that this approach can generate long-lasting immune responses, directing the immune system to recognize cancer. We believe this work can form a foundation for the development of neoantigen vaccines in kidney cancer."
References
1. Cancer vaccine shows promise for patients with stage III and IV kidney cancer. News release. Dana-Farber Cancer Institute. February 5, 2025. Accessed February 5, 2025. Https://www.Dana-farber.Org/newsroom/news-releases/2025/cancer-vaccine-shows-promise-for-patients-with-stage-iii-and-iv-kidney-cancer
2. Braun DA, Moranzoni G, Chea V, et al. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature. Published online February 5, 2025. Doi:10.1038/s41586-024-08507-5
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