Tag: Clinical Trials

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.

neoantigen[2]
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:

“Moonshots” and More: How We’re Developing Personal Cancer “Cures” through Precision Medicine

In President Barack Obama’s final State of the Union address, he emphasized the “moonshot” need to cure cancer. At Weill Cornell Medicine and NewYork-Presbyterian Hospital, we are actively working towards that goal.

420_Dr. David Nanus with patient Irene Price 8 x 12
Irene Price and Dr. David Nanus, Chief, Hematology and Medical Oncology at Weill Cornell Medicine

Through our use of gene sequencing and precision medicine, we are transforming the way cancer is characterized and treated. Using a multidisciplinary approach and the EXaCT-1 test, here at the Weill Cornell Genitourinary (GU) Oncology Program, we are able to sequence the genes of advanced stage cancer patients. We can then narrowly tailor personalized treatment regimens based on the genetic makeup of a patient’s tumor which indicates whether a cancer is likely to respond to a particular treatment therapy.

Irene Price came to Dr. David Nanus, Chief of the Division of Hematology and Medical Oncology, with metastatic bladder cancer, and had more than 20,000 genes sequenced with the EXaCT-1 test. Dr. Nanus and his colleagues determined that the reason she wasn’t responding to prior treatment rested in a specific genetic mutation within her tumor. As a result, the team was able to prescribe a personalized treatment regimen – one more often used in the treatment of breast cancer.

The results were life changing. It caused her cancer to completely disappear. According to Price, “I’ve had college graduations that I wouldn’t have had, weddings that I wouldn’t have had, and the birth of great grandchildren that I wouldn’t have had.”

Learn more about our personalized approach to cancer care in a two-part series on NY1:

Part 1: “Gene Sequencing Effort Helps Pinpoint Cancer Treatments”

Part 2: “Tailored Cancer Treatments Fit Doctors’ New Approach”


To make an appointment with one of our clinicians, please call 646-962-2072.

Dr. Tagawa Presents Updated Results of ATL101 at AACR

At the annual American Association for Cancer Research in Washington, DC last week, Dr. Scott Tagawa presented updated combined analysis of 4 Phase I and Phase II studies involving 114 patients treated with ATL101. The analysis demonstrated that PSMA imaging might be used to predict the response to ATL101 radioimmunotherapy.ATL101 is a new targeted radiotherapy experimental drug for treating prostate cancer. ATL101 combines the humanized J591 monoclonal antibody targeting prostate-specific membrane antigen (PSMA) plus the Lutetium-177 radioisotope, creating the first tumor-specific delivery system able to target radiation to radio-sensitive prostate cancer cells wherever they are in the body.

From the sponsor’s press release:

14 patients were evaluable for semi-quantitative analysis of planar gamma images acquired after injection of ATL101 (35 patients from phase I at dose of 10-75 mCi/m²; 47 patients from Phase II at dose of 65-70 mCi/m² and 39 patients from phase I with a fractionated schedule at dose of 40-90 mCi/m²). 22 patients were also evaluable after injection of Indium-111 labeled J591 and treatment by Yttrium-90 labeled J591 at dose of 5-20mCi/m². Patients were sorted into 3 groups: low PSMA expression group included one third of patients, with no uptake (18%) or with weakly positive images (16%); high PSMA expression group included one half of patients, with tumor image as intense (26%) or more intense (24%) than liver. The 16 % remaining patients had intermediate uptake.

Significant correlation was found between higher PSMA expression (high vs. low) and higher response rates (RR) to treatment defined as >30% decline in PSA (RR=32% vs. 12.5%, p=0.01). RR was itself significantly correlated to longer survival. An association between PSMA expression by imaging and reduction in circulating tumor cell counts was also found (p=0.07). Further studies will examine quantitative molecular imaging with anti-PSMA PET/CT as recently published in animal models (Morris et al, 2013 ASCO Genitourinary Cancers Symposium).

Click here to read the complete press release.