Tag: Cancer Treatment

Cancer: A Wolf in Sheep’s Clothing

Immunotherapy wolf in disguiseCancer cells can be pretty sneaky, altering their make-up or microenvironment to avoid detection by our body’s immune system. As a result, the immune system, which is designed to fight off “invaders,” can’t detect cancer as foreign and doesn’t have its guard up.

Earlier this month, NewYork-Presbyterian Hospital kicked off a new ad campaign highlighting how immunotherapy is working to change just that. Immunotherapy treatments are designed to help activate the immune system and kick it into high gear, helping it fight the very cancer it was previously unable to detect.

https://www.youtube.com/watch?v=NmtGKer20aY

New scientific discoveries happening right here at Weill Cornell Medicine are making this possible. Our physician-scientists and researchers at the Meyer Cancer Center have found ways to help the immune system better recognize and destroy cancer cells by designing new immunotherapy drugs, cancer “vaccines,” and combination treatments. Through precision medicine and an individualized approach to cancer care, we are developing new ways to treat cancer more successfully than ever before. And, we’re accomplishing these results with less toxicity.

Over the past decade, the U.S. Food and Drug Administration (FDA) has approved several new immunotherapy drugs for advanced cancers. At the Weill Cornell Genitourinary (GU) Oncology Program, we have greatly contributed to the efforts to obtain FDA-approval for immunotherapies for GU cancers, including kidney cancer, bladder cancer, and prostate cancer.

For kidney cancer, we have been involved in many studies of drugs utilizing the immune system to fight cancer, including the phase 2 clinical trial that formed the basis for the large trial leading to the FDA approval and general availability of nivolumab (Opdivo) for renal cell carcinoma. Nivolumab is an immunotherapy that works by allowing the body’s existing immune system to kill tumors. Our team is now working on ways to improve this drug and other types of drugs.

For bladder and other urothelial cancers, we have been instrumental in the development of several antibodies that can be used with and without chemotherapy. Sacituzumab Govitecan (IMMU-132), an antibody-drug conjugate, has had remarkable preliminary activity. It works by leveraging the immune system and bringing a powerful drug directly to the interior of cancer cells in order to kill them from the inside out. We are continuing to use this drug as well as other immunotherapeutic agents to improve outcomes for patients with these types of cancer.

Based upon several scientific properties, prostate cancer is a good tumor type for immunotherapy, and in fact, the first therapeutic cancer vaccine (used to treat cancer rather than prevent cancer) was approved for prostate cancer. At Weill Cornell Medicine, exploiting the immune system remains a focus in fighting prostate cancer, with a number of ongoing and upcoming clinical trials. Weill Cornell Medicine continues to be a worldwide leader in work with monoclonal antibodies, which are proteins (like a “key”) that very specifically target cancer cells (with a specific “lock” that is not present on normal cells). In particular, our work with antibodies against prostate-specific membrane antigen (PSMA) has led to the development of several targeted therapies for prostate cancer. These antibodies can be linked to powerful radioactive particles or drugs that seek out prostate cancer cells (like a smart bomb). For men with prostate cancer whose PSAs rise despite hormonal therapy, we are leading a study of targeted radioimmunotherapy that aims to prevent metastatic disease. In addition, the antibody itself may be able to generate an immune response in prostate tumors and lead to clearance of circulating tumor cells. We are also working on developing vaccines for men with rising PSAs following surgery or radiation.

We continue to examine many promising, cutting-edge immunotherapies through our robust clinical trial program. Click the below links to learn more about eligibility and open clinical trials across the spectrum of GU cancers:

Open Immunotherapy-Based Clinical Trials

Prostate Cancer

Kidney, Bladder and Urothelial Cancers

To search our complete list of our open clinical trials, click here.

Second-Line Treatments for Metastatic Kidney Cancer

Metastatic renal cell carcinoma (RCC) has traditionally been treated with the second-line chemotherapeutic agent everolimus, but two other drugs have been newly identified as better options that can give months or even years of life to patients with metastatic RCC. Two studies led by Dr. Robert J. Motzer of Memorial Sloan Kettering Cancer Center have recently shown that nivolumab and cabozantinib each improve survival of patients compared to those receiving the traditional everolimus treatment. Nivolumab in particular shows great promise, with 25% of patients responding to the drug versus 5% with everolimus, and a median survival of 26 months compared to 19.6 for everolimus- such a dramatic difference that the study was stopped early to allow the patients on everolimus to switch to nivolumab.
Nivolumab belongs to a class of cancer drugs called immune checkpoint inhibitors that are designed to turn the patient’s immune system against the cancer cells. Normally, the immune system is able to recognize cells like cancer cells that are growing abnormally. The immune system is then able to send a signal to the cancer cells to self-destruct, blocking the progression of the cancer. As cancers progress, many develop ways of avoiding being spotted by the immune system, preventing the patient’s body from fighting off the cancer. Immune checkpoint inhibitors like nivolumab unmask the cancer cells and enable the immune system fight back again. This is the first time an immune checkpoint inhibitor has been shown to improve survival of patients with metastatic RCC and will likely result in the approval of nivolumab as a new second-line agent for treating this disease.
More information can be found at the New England Journal of Medicine or The New York Times.

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.