Weill Cornell Researchers: Encouraging Results from J591 Study

Dr. Tagawa
Dr. Tagawa

Weill Cornell researchers recently published findings from a Phase II study of the lutetium-177-labeled monoclonal antibody J591 (called Lu-J591).

J591 is a man-made monoclonal antibody that is able to recognize a protein antigen (PSMA) expressed on virtually all prostate cancer cells, and more so in men with treatment-resistant metastatic disease. When a tiny tag of radioactive material is attached to the J591 antibody, that specifically targets prostate cancer cells, and delivered systemically this is known as “radioimmunotherapy.” Dr. Scott Tagawa and colleagues at Weill Cornell have been conducting clinical trials of the precision radioimmunotherapeutic J591 to determine its ability to eradicate prostate cancer cells.

In the recently published study, 47 prostate cancer patients with PSA progression after hormonal therapies with or without chemotherapy were treated with Lu-J591. 10.6 percent experienced more than 50% PSA decline, and 36.2% experienced more than 30% decline. Among those treated at the maximum tolerated dose, 46.9% had more than 30% PSA decline. Furthermore, 75% of patients with radiographically measurable disease had some measure of disease control; 67% of those assessed for circulating tumor cells had more than 50% decline in tumor cell counts 4 to 6 weeks after treatment.

The researchers concluded that a single dose of Lu-J591 was well tolerated and they found a measurable response rate. The authors conclude that Lu-J591 is a promising new therapeutic strategy to explore.

Click here to read the published abstract. Click here to read an article about the study and the findings.

Weill Cornell Researchers Create Device to Collect Living Prostate Tumor Cells; Potential to Inform Development of New Drugs

Cancer metastases (spreading from the initial cancer tumor to other parts of the body) account for the majority of cancer-related deaths because of poor responses to anti-cancer therapies.

Researchers at Weill Cornell Medical College, in collaboration with engineers from Cornell University in Ithaca, NY, have created a new device that searches the blood for living, circulating tumor cells. The device allows researchers to capture and molecularly characterize circulating tumor cells (CTCs) isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. This new device will allow physicians to monitor drug response at the cellular level, which will potentially allow physicians to tailor prostate cancer treatments to an individual patient. The device is the first functional assay of a microtubule-targeting agent on living circulating tumor cells microfluidically extracted from patient blood.

The researchers  include Dr. Brian Kirby at Cornell University and  Dr. Paraskevi Giannakakou, Dr. Neil Bender, Dr. Scott Tagawa and Dr. David Nanus at Weill Cornell Medical College.

Background

Circulating tumor cells are prostate cancer cells which have escaped from prostate tumors (from the prostate, bone, or other areas) and are circulating in blood.  The FDA has cleared a specific type of test to enumerate (or count) the number of these cells in a tube of blood, called the CellSearch test.  The advantage of this test is that it has been well studied at many centers and has been validated to yield prognostic information.  However, this test is not very sensitive; men with metastatic prostate cancer may have no detectable cells.  In addition, this test is not specific to prostate cancer – the same test also picks up different cells (it is also cleared for breast and colon cancer).

The New Device

The collaborating researchers at Weill Cornell and Cornell University developed a new test called the “Geometrically Enhanced Differential Immunocapture” device. The device has been optimized based upon flow and size characteristics of prostate cancer cells.  Importantly, the device uses additional technology developed at Weill Cornell, a monoclonal antibody against Prostate Specific Membrane Antigen (PSMA).  The anti-PSMA antibody called J591, developed by Dr. Neil Bander in the Weill Cornell Department of Urology,  specifically recognizes the PSMA protein which is present on the surface of virtually all prostate cancer cells.  The combined technology has allowed Weill Cornell researchers to collect and analyze more prostate cancer cells than the standard device.

In addition to prognostic information, it is hoped that the capture and analysis of CTCs may serve as a type of “liquid biopsy” to allow researchers to gain information about a patient’s tumor.  Initial work has led to promising results in the ability to predict future responses to chemotherapy based upon a blood test prior to the drug or after only 1 dose.

The authors write, “these measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents.”

Click here to read the published research paper.

Scientists Discover New Prostate Cancer Subtype

Researchers at Weill Cornell Medical College, collaborating with researchers at the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute, have uncovered a distinct molecular subtype of prostate cancer, which is prevalent among 15% of men with the disease.

In the study, published online May 20 in the journal Nature Genetics, investigators describe how they discovered novel mutations in the SPOP (“S-pop”) gene in numerous patient tumors, saying this alteration is thus far unique to prostate cancer and represents a distinct molecular class that might assist in cancer diagnosis and treatment. Researchers suspect the mutations alter the way cells tag proteins for degradation, leading to an accumulation of dangerous molecules that drive the growth of cancer, perhaps from the beginning.

This type of mutation is unique to prostate cancer. By targeting the mutations in the SPOP gene, a new class of cancer diagnosis and treatment can be developed.

This finding adds to a string of discovery of other genes linked to prostate cancer over the years by this team of investigators, the totality of which is painting a comprehensive picture of how genetic alterations contribute to prostate cancer — the most common cancer in men aside from skin cancer, accounting for the second leading cause of cancer deaths.

Click here to read the published research paper.