Gene editing reverses Huntington's in mouse model

This is a concrete example, not yet clinical, of what can be done with CRISPR/Cas9 gene Read more

Urine tests for prostate cancer could reduce biopsies

Urine RNA tests could reduce the number of biopsies by giving a preview of a cancer's aggressiveness. Featuring Martin Sanda and Carlos Read more

Mitochondrial blindness -- Newman's Emory story

Neuro-ophthalmologist Nancy Newman’s 2017 Dean’s Distinguished Faculty Lecture and Award were unexpectedly timely. Her talk on Tuesday was a tour of her career and mitochondrial disorders affecting vision, culminating in a description of gene therapy clinical trials for the treatment of Leber’s hereditary optic neuropathy. The sponsor of those studies, Gensight Biologics, recently presented preliminary data on a previous study of their gene therapy at the American Academy of Neurology meeting in April. Two larger trials Read more

Suresh Ramalingam

Cancer immunotherapy responses in the clinic: T cell revival as predictor

In lung cancer patients who were taking immunotherapy drugs, testing for revived immune cells in their blood partially predicted whether their tumors would shrink. The results were published online by PNAS on April 26.

This finding comes from a small study of 29 patients, who were being treated at Winship Cancer Institute of Emory University with drugs blocking the PD-1 pathway, also known as checkpoint inhibitors.

The study supports a straightforward idea: if tumor-specific CD8 T cells appear to respond to the drug (nivolumab, pembrolizumab or atezolizumab), that’s a good sign. This avenue of investigation may also help researchers figure out why some patients do not benefit from checkpoint inhibitor drugs, and how to combine those drugs with other treatments to increase response rates.

While looking for activated immune cells in the blood is not yet predictive enough for routine clinical use, such tests could provide timely information. Monitoring the immune response could potentially help oncologists and patients decide, within just a few weeks of starting immunotherapy drugs, whether to continue with the treatment or combine it with something else, says co-senior author Suresh Ramalingam, MD, Winship’s deputy director.

“We hypothesize that re-activated CD8 T cells first proliferate in the lymph nodes, then transition through the blood and migrate to the inflamed tissue,” says Rafi Ahmed, PhD, director of the Vaccine Center and a Georgia Research Alliance Eminent Scholar. “We believe some of the activated T cells in patients’ blood may be on their way to the tumor.”

The rest of the Emory Vaccine Center/Winship Cancer Institute press release is here. A few additional points: Read more

Posted on by Quinn Eastman in Cancer, Immunology Leave a comment

Revived T cells still need fuel

Cancer immunotherapy drugs blocking the PD-1 pathway – known as checkpoint inhibitors – are now FDA-approved for melanoma, lung cancer and several other types of cancer. These drugs are often described as “releasing the brakes” on dysfunctional T cells.

A new study from Emory Vaccine Center and Winship Cancer Institute researchers shows that even if the PD-1-imposed brakes are released, the tumor-specific T cells still need “fuel” to expand in numbers and restore effective immune responses. That fuel comes from co-stimulation through a molecule called CD28.

The results were published Thursday by the journal Science.

Despite the success of PD-1-targeting drugs, many patients’ tumors do not respond to them. The study’s findings indicate that CD28’s presence on T cells could be a clinical biomarker capable of predicting whether drugs targeting PD-1 will be effective. In addition, the requirement for CD28 suggests that co-stimulation may be missing for some patients, which could guide the design of combination therapies.

For the rest of our press release and quotes from authors Rafi Ahmed, Alice Kamphorst and Suresh Ramalingam, please go here. For some additional links and thoughts on PD-1 and CD28, read on:

Read more

Posted on by Quinn Eastman in Cancer, Immunology Leave a comment

Lung cancer clinical trial shows treatment promise

Advanced non-small cell lung cancer (NSCLC) is a challenging disease to treat. More than 200,000 new cases of lung cancer are diagnosed each year, and 85 percent to 90 percent of diagnosed lung cancers fall into the non-small cell type.

A new strategy for treating NSCLC that increases the effectiveness of standard chemotherapy in patients with advanced stage disease has been found by Emory researchers. Recent advances in treatment result in improvement in patient survival noted for all stages of NSCLC.

Saresh Ramalingam, MD

Saresh Ramalingam, MD

Lead investigator Suresh Ramalingam, MD, associate professor of hematology and medical oncology at Winship Cancer Institute of Emory University, along with a consortium of academic institutions that is supported by the National Cancer Institute, published the positive results in The Journal of Clinical Oncology.

In the clinical trial, Emory scientists added a cancer-fighting compound that is used to treat a specific type of lymphoma to standard lung cancer chemotherapy, resulting in an increase in positive response rates in NSCLC patients.

The addition of vorinostat, a compound that affects the function and activity of DNA and various other proteins, to standard chemotherapy treatment of carboplatin and paclitaxel, increased positive response rates in patients from 12.5 percent to 34 percent in a clinical trial of 94 patients with metastatic non-small cell lung cancer.

Vorinostat may be affecting histones, which are spool-like proteins around which the cell’s DNA is wound. These proteins are important for cell division. We believe these molecular effects could enhance the efficacy of carboplatin and paclitaxel, respectively.

Vorinostat is part of an emerging class of anti-tumor agents that interfere with enzymes known as histone deacetylases (HDAC). Inhibiting these enzymes increases the level of acetylation, a modification of proteins in the cell. Vorinostat is sold by Merck as Zolinza and was approved by the FDA in 2006 to treat cutaneous T cell lymphoma.

Ramalingam says this exciting data will have to be further evaluated in confirmatory phase III studies before they can be adopted in routine use. However, HDAC inhibitors can now be considered among the leading targeted agents under evaluation for the treatment of non-small cell lung cancer.

Posted on by Vince Dollard in Cancer Leave a comment