What are Cancer Neoantigens? The Link Between Neoantigens and Immunotherapy

By Bishoy Faltas, M.D.

Our immune system has evolved over time to enable us to fight infections. Our bodies need to differentiate between our own cells (self) and cells from bacteria and viruses (non-self) in order to mount an effective attack to eliminate the invaders. In order to do that, our immune system has learned to recognize fragments of foreign proteins, which carry a specific sequence that marks them as “targets” for the immune system. We call these antigens.

Cancer cells thrive because they hide from the immune system, but their disguise is not perfect. Cells typically become cancerous because of changes in their genetic makeup. These same changes can result in proteins that the immune system is able to recognize as foreign. These are called neoantigens, and refer to new cancer antigens that cue the immune system to attack the cancer and eliminate it.

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New sequencing technologies enable us to detect new cancer antigens unique to each patient.
The immune system just needs a little help to make this happen. To tip the balance in favor of the immune system, we now use drugs called immune checkpoint inhibitors. These unleash the power of the immune system to attack the tumor. A good way to think about it is as “releasing the brakes” off the immune response. This approach to treatment is very promising for bladder cancer, especially when other treatments have failed to stop the cancer from progressing or metastasizing to other organs.

To understand which patients are most likely to respond to these immune checkpoint inhibitors, we conducted a study examining the neoantigens in bladder cancer patients at Weill Cornell Medicine. Our analyses found many differences in the neoantigens between untreated tumors and advanced tumors that had previously been treated with chemotherapy from advanced chemotherapy-resistant bladder cancers. More details on our findings can be found here:

In the future, we are hoping to use neoantigens as biomarkers that tell us which patients are most likely to respond to specific immunotherapies. A form of precision medicine, this will help us to narrowly tailor our treatment approach to each patient.

Some of our current immunotherapy treatments for people with bladder cancers include:

Kidney Cancer – It Takes a Team

By Ana M. Molina, M.D.

Each year, about 63,000 people in the United States are newly diagnosed with kidney cancer. Whether you’re still undergoing testing to determine whether you have kidney cancer or have already been diagnosed, you may be wondering where to turn next and who to trust.

Kidney cancer requires a multidisciplinary, team-based approach to treatment and that includes you as a key member of the team. For advanced cancers, your medical oncologist should act as your quarterback to help you navigate your next play. Your medical oncologist will work with you and recommend treatments and next steps based on your wishes and goals for treatment. The oncologist will account for factors such as the type of kidney cancer you have, the size and placement of the tumor and whether the cancer has spread to other organs throughout your body. This can also be referred to as the process of cancer staging and management.

From the time of your diagnosis and throughout the course of your treatment, you will be meeting with a variety of specialists who all provide different expertise.

Kidney Cancer_It Takes a Team

In honor of March being National Kidney Cancer Awareness Month, here’s an overview of all the players:

Urologist: Urologists specialize in diseases of the urinary tract, including the kidneys, and the male reproductive organs. Within this field, there are sub-specialists who specifically focus on urological cancers. A urologic surgeon who specializes in oncology will be the one who determines whether the tumor can be surgically removed. Based on the size and placement of the tumor, all or part of the kidney may be removed. If only the cancerous part of the kidney is removed, it is called a partial nephrectomy. If the entire kidney is removed, the procedure is called a radical nephrectomy. Whenever possible, it is advantageous to have a partial nephrectomy in order to save nephrons – the kidneys’ filtering units—and preserve kidney function. Following surgery, you will meet with the urologist to review the pathology results and discuss next steps.

Medical Oncologist: This doctor specializes in monitoring and treating your kidney cancer using medical intervention. A medical oncologist can recommend a wide-range of treatment options such as clinical trials, chemotherapy, immunotherapy, combination therapies and targeted therapies. At the Weill Cornell Genitourinary (GU) Oncology Program, we also offer personalized care in the form of precision medicine. This involves tumor profiling to analyze the genetic makeup of your kidney cancer. Based on the results of this analysis, we’re able to select treatment choices that most closely match the vulnerabilities of your specific tumor(s). The medical oncologist will refer you to a urologic surgeon or radiation oncologist if these interventions will offer the best course of treatment for your specific situation.

Radiation Oncologist: This specialist delivers cancer treatment using x-rays and other forms of radiation to treat metastatic kidney cancers. At Weill Cornell, we currently offer clinical trials that combine immunotherapy and radiation which has been shown to have an abscopal effect, meaning that this combined treatment has been able to activate the body’s immune system in order to eliminate tumors that weren’t directly targeted by the radiation.

Radiologist and Interventional Radiologist: Radiologists are the doctors who review imaging tests ordered by your urologist or medical oncologist to determine the location of your cancer and whether it has spread. Imaging tests you may receive include: computed tomography (CT) scans, magnetic resonance imaging (MRI), positron emission tomography (PET), ultrasonography and x-rays. A sub-specialty within radiology, the interventional radiologist is the person who will use image-guided tests to conduct minimally invasive procedures. For example, the interventional radiologist will biopsy organs and tissue in order to collect samples from your tumor. These samples will be examined by pathologists and may ultimately be used for precision medicine and to test out which treatments may be most beneficial to your specific cancer.

Nephrologist: This is the doctor who specializes in treating kidney disease and preserving your remaining kidney function. Nephrologists also work with your healthcare team to help manage other risk factors for kidney failure such as diabetes and hypertension, and to ensure you’re on a kidney-protective regimen. Since many medications are “cleared” by the kidneys, this may involve changing your medications to reduce the stress on the kidneys to filter these medications out of your body as waste.

Palliative Care Physician and Social Worker: Palliative care is often wrongly interpreted as a synonym for end-of-life care and hospice. The field of palliative care, or supportive medicine, is more accurately described as the services that help improve quality of life. It is beneficial for this team to get involved early, as these experts help alleviate some of the symptoms of kidney cancer and its treatment, while even helping to extend life. A palliative care physician can help manage pain and help to reduce uncomfortable side effects such as diarrhea and nausea. They also provide counseling and other therapeutic interventions to help people cope with the emotional impact a cancer diagnosis can have on patients and their loved ones.

At the Weill Cornell GU Oncology Program, we have weekly tumor board meetings in which many of the specialists listed above all meet together to discuss our patients’ care. This close collaboration with experts across kidney cancer sub-specialty areas helps ensure that our patients are receiving the best, most comprehensive and cutting-edge treatment. Because we have a shared system of medical records across the Weill Cornell Medicine healthcare network, communication between our physicians is integrated and seamless.

We understand that it’s not only your medical team that provides support and care during the course of cancer treatment. Our Kidney Cancer Support Group brings together other patients, caregivers and loved ones so that you’re part of a community that “has been there” and understands what you’re going through.

Partnering to Detect Prostate Cancer

By Scott Tagawa, M.D.

Prostate cancer comes in many forms. Some tumors, however anxiety producing, are slow-growing tumors and simply require monitoring. And then, there are aggressive tumors that need treatment as soon as possible. Some times these aggressive tumors even spread microscopically prior to surgery or radiation without us knowing. By finding better ways to detect the types of prostate cancers that need to be treated, and as early as possible, we increase our cure rates and the number of people we’re able to treat effectively, while simultaneously minimizing interventions for those who don’t need them.

So where do we begin when it comes to detecting these aggressive tumors? And differentiating them from their less-aggressive counterparts?

Molecular imaging holds many of these answers, particularly for prostate cancer, as it offers a non-invasive way to detect the presence of cancer and distinguish between aggressive and non-aggressive sub-types. At the Weill Cornell Genitourinary (GU) Oncology Program, we’ve had a longstanding expertise in using molecular imaging to better diagnose and treat cancer.

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(Left) A traditional bone scan only shows one small possible site of metastases in the shoulder region of the bone, compared with the molecular imaging scan of the same patient (right) which indicates many metastases throughout the body.

Through our collaboration across multidisciplinary teams and with industry partners, at our academic medical center we have developed several imaging compounds, such as 99Tc-MIP 1404. This is a radiotracer used to more clearly “see” prostate cancer cells through their expression of the prostate-specific membrane antigen (PSMA). PSMA is a key biomarker in prostate cancer that is present on nearly all tumors. By using this target as a tracer, we can sometimes detect sites of tumors that were not evident on standard types of scans. In addition, the level of PSMA evident in prostate cancer cells can indicate whether the cancer is of a higher grade, more aggressive tumor within the prostate. Our patients were among the first to have received access to this technology. We’re currently leading a clinical trial that is pivotal to the FDA ultimately approving the widespread use of 99Tc-MIP 1404 to detect prostate cancer and help us ultimately determine the best course of treatment.

In part, due to this collaborative work, we were able to recruit the inventor of some of these imaging compounds, Dr. John Babich, to Weill Cornell Medicine in 2013. Collaboration is critical to scientific progress, and we are proud to be building on these accomplishments and forming new strategic partnerships in order to bring scientific discoveries to our patients more quickly than we would be able to if everyone worked in isolation.

It was recently announced that Weill Cornell Medicine has now formed a new research collaboration with Senior Scientific, LLC to investigate using non-radioactive magnetic nanoparticles to detect and diagnose prostate cancer. The combination of molecular nuclear medicine imaging with the magnetic relaxometry (MRX) technology may lead to improvements for many of the thousands of men facing the diagnosis of prostate cancer. We look forward to working with Dr. John Babich to bring MRX technology to our patients and will keep you apprised of research progress.