Features | Partner Sites | Information | LinkXpress
Sign In
JIB
BioConferenceLive
GLOBETECH PUBLISHING

Cancer Treatment Shown to Boost Immune System

By BiotechDaily International staff writers
Posted on 11 Jun 2012
Two clinical trials evaluating experimental drugs aimed at restoring the immune system’s ability to target and fight cancer have shown promising early results in patients with advanced non-small-cell lung cancer, melanoma, and kidney cancer. More than 500 patients were treated in the studies of two drugs that target the same immune-suppressive pathway, and the investigators say there is enough evidence to support wider testing in larger groups of patients.

Findings of the phase I clinical trials will be published online June 2, 2012, in the New England Journal of Medicine (NEJM) and presented at the 2012 annual meeting of the American Society of Clinical Oncology, held in June 2012 in Chicago (IL, USA). “Based on the positive response rates to these drugs and longevity of many of these responses, we believe that new clinical trials should move forward,” said Suzanne Topalian, MD, professor of surgery and oncology at Johns Hopkins Kimmel Cancer Center (Baltimore, MD, USA). Early analysis shows that among responding patients who were monitored for more than one year, responses were sustained for more than one year in two-thirds of those treated on one trial and in half of those in the other trial.

In the immune-based therapies assessed in the two clinical trials, both manufactured by Bristol-Myers Squibb (New York, NY, USA), the goal is not to destroy cancer cells directly, but to block a pathway that protects tumor cells from immune system components ready and able to fight cancer.

The pathway includes two proteins called programmed death-1 (PD-1), expressed on the surface of immune cells, and programmed death ligand-1 (PD-L1), expressed on cancer cells. When PD-1 and PD-L1 combine, they form a biochemical “shield” protecting tumor cells from being destroyed by the immune system. Another protein involved in the pathway, and also expressed by cells in the immune system, programmed death ligand -2 (PD-L2), was first discovered by Johns Hopkins investigators.

To make cancer cells more susceptible to attack by the immune system, investigators tested each of two drugs--BMS-936558, which blocks PD-1, and BMS-936559, which blocks PD-L1--in separate clinical trials conducted at multiple US hospitals. The drugs are given intravenously in an outpatient clinic every two weeks, and patients can remain on the treatment for up to two years.

The PD-1 blocking drug was tested in 296 patients with various advanced cancers who had not responded to standard therapies. Of those patients receiving the anti-PD-1 therapy, 240 who started treatment by July 2011 were analyzed for tumor response. Significant tumor shrinkage was seen in 14 of 76 (18%) non-small-cell lung cancer patients, 26 of 94 (28%) melanoma patients, and 9 of 33 (27%) kidney cancer patients.

In this trial, some patients experienced stable disease for six months or more, including 5 of 76 (7%) lung cancer patients, 6 of 94 (6%) melanoma patients and 9 of 33 (27%) kidney cancer patients. The investigators reported that additional clinical studies will be needed to determine the agents potential impact on survival. “This level of response in patients with advanced lung cancer, which is typically not responsive to immune-based therapies, was unexpected and notable,” stated Julie Brahmer, MD, associate professor of oncology at Johns Hopkins.

The anti-PD-L1 therapy also showed responses among 207 treated patients. Five of 49 (10%) non-small-cell lung cancer patients, nine of 52 (17%) melanoma patients, and two of 17 (12%) kidney cancer patients responded. “The positive results from both drugs give us a good indication that the PD-L1/PD-1 pathway is an important target for cancer therapy,” remarked Dr. Topalian.

The anti-PD1 therapy caused serious toxicities in 41 of 296 (14%) patients. Many of the toxicities were immune-related, including colon inflammation, thyroid abnormalities, and three deaths from pneumonitis (lung inflammation). The investigators reported that they are working with colleagues across the United States to develop better techniques for early detection and effective treatment of pneumonitis. Other less severe toxicities included fatigue, itching, and rash. The anti-PD-L1 therapy caused 9% serious toxicities and no deaths.

Among patients receiving anti-PD-1, tumor samples collected from 42 study patients before they received the experimental therapy were evaluated at Johns Hopkins Medicine for molecular markers that may correlate with clinical response. The investigators found PD-L1, the partner protein to PD-1, in 25 of the 42 samples. Nine of the 25 patients with PD-L1-positive tumors experienced tumor shrinkage as compared with none of the patients with PD-L1 negative tumors.

“These early results indicate that PD-L1 expression in pretreatment tumor biopsies may correlate with clinical response to anti-PD-1 therapy, but more work needs to be done to confirm this, “ said Dr. Brahmer.

The two therapies targeting the PD-1/PD-L1 pathway are in the same class of so-called “antibody therapies,” which are comprised of proteins that target and bind to specific molecules on the cell surface. Other antibody therapies include such drugs as Erbitux, Herceptin, and Rituxan. “We have just scratched the surface of laboratory and clinical research on these drugs,” said Dr. Topalian.

The scientists ultimately foresee boosting the effectiveness of the therapy by combining it with other anticancer agents, including cancer vaccines.

Related Links:

Johns Hopkins Kimmel Cancer Center
Bristol-Myers Squibb




comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: Microcomputed tomography images (top) and histology images (bottom) of the knees of mice fed a very high fat diet containing omega-3 fatty acid supplement (left) or only omega-6 fatty acids (right) after a knee injury. The omega-6 diet showed abnormal bone remodeling and calcified tissue formation in the joint (white arrow). The omega-6 diet also showed significant loss of cartilage (red staining, yellow arrowhead) and increased joint inflammation (Photo courtesy of Duke University).

Dietary Omega-3 Fatty Acids Moderate Severity of Osteoarthritis in a Mouse Model

Researchers working with an osteoarthritis (OA) obese mouse model found that the fat content of the animals' diet contributed more to the development or arrest of OA than did body weight.... Read more

Drug Discovery

view channel
Image: Molecular rendering of the crystal structure of parkin (Photo courtesy of Wikimedia Commons).

Cinnamon Feeding Blocks Development of Parkinson's Disease in Mouse Model

A team of neurological researchers has identified a molecular mechanism by which cinnamon acts to protect neurons from damage caused by Parkinson's disease (PD) in a mouse model of the syndrome.... Read more

Business

view channel

A Surge in IPOs Revitalize Investments for the Global Pharma and Biotech

Anti-infective drugs, oncology, and pharmaceutical contract laboratories attract the most investment up to now. The intensified private equity and venture capital (PEVC) deal activity in the global healthcare industry during the recession years, 2008–2010, witnessed a waning post-2010. However, the decline in deals... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.